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Biomedical subjects

L Gutmann

Publications and source records attributed to L Gutmann.

At least 55 records · Page 3Linked to original sources
PubMed1998

Colonization by Acinetobacter baumanii in intensive-care-unit patients.

We prospectively studied the value of systematic rectal swabs performed for the detection of colonization and the prediction of infections by Acinetobacter baumanii in 751 consecutive patients admitted to five intensive-care units (ICUs) over an 8-month period. Gastrointestinal tract colonization was found in 8.7% of ICU admissions. The positive and negative predictive values of rectal swabs for the detection of subsequent infection were 17% and 99%, respectively. Sensitivity and specificity were 55% and 93%, respectively. We also determined the comparative values of rectal or nasal swabs and skin cultures for the detection of A baumanii colonization in 25 patients already colonized or infected with A baumanii. The combination of rectal and nasal swabs was positive in 20 (80%) of 25. The results of the present study suggest that detection of gastrointestinal tract A baumanii colonization is not an accurate predictor of subsequent A baumanii infection and that combined rectal and nasal swabs might be used for the detection of A baumanii colonization in ICU patients.

Acinetobacter↗
PubMed1998

In vitro activity of sanfetrinem and affinity for the penicillin-binding proteins of Streptococcus pneumoniae.

Against penicillin-susceptible pneumococci, the activity of sanfetrinem was similar to those of penicillin, amoxicillin, cefotaxime, imipenem, and meropenem, while against penicillin-resistant strains, sanfetrinem and the carbapenems exhibited superior activity (MICs at which 90% of strains are inhibited, < or =1 microg/ml). PBP 1a in the penicillin-susceptible strain and PBP 1a and PBP 2b in the more resistant isolates seemed to be the essential penicillin-binding proteins for imipenem and sanfetrinem.

Anti-Bacterial Agents↗
PubMed1998

Acquisition of five high-Mr penicillin-binding protein variants during transfer of high-level beta-lactam resistance from Streptococcus mitis to Streptococcus pneumoniae.

Penicillin-resistant isolates of Streptococcus pneumoniae generally contain mosaic genes encoding the low-affinity penicillin-binding proteins (PBPs) PBP2x, PBP2b, and PBP1a. We now present evidence that PBP2a and PBP1b also appear to be low-affinity variants and are encoded by distinct alleles in beta-lactam-resistant transformants of S. pneumoniae obtained with chromosomal donor DNA from a Streptococcus mitis isolate. Different lineages of beta-lactam-resistant pneumococcal transformants were analyzed, and transformants with low-affinity variants of all high-molecular-mass PBPs, PBP2x, -2a, -2b, -1a, and -1b, were isolated. The MICs of benzyl-penicillin, oxacillin, and cefotaxime for these transformants were up to 40, 100, and 50 microg/ml, respectively, close to the MICs for the S. mitis donor strain. Recruitment of low-affinity PBPs was accompanied by a decrease in cross-linked muropeptides as revealed by high-performance liquid chromatography of muramidase-digested cell walls, but no qualitative changes in muropeptide chemistry were detected. The growth rates of all transformants were identical to that of the parental S. pneumoniae strain. The results stress the potential for the acquisition by S. pneumoniae of high-level beta-lactam resistance by interspecies gene transfer.

Amino Acid Sequence↗
PubMed1998

Genetically related human immunodeficiency virus type 1 in three adults of a family with no identified risk factor for intrafamilial transmission.

A small number of cases of human immunodeficiency virus (HIV) infection have been reported in individuals with no identified risk factors for transmission. We report on the seroconversion of the 61-year-old mother and the subsequent finding of HIV seropositivity in the 66-year-old father of a 31-year-old AIDS patient. Extensive investigation failed to identify any risk factor for intrafamilial transmission. We conducted a genetic analysis and determined the amino acid signature patterns of the V3, V4, and V5 hypervariable domains and flanking regions in the HIV-1 gp120 env gene of 26 clones derived from proviral DNA in peripheral blood mononuclear cells of the members of the family. env sequences of the viruses isolated from the patients were compared with sequences of HIV-1 subtype B viruses from Europe and local field isolates. Phylogenetic analysis revealed that the sequences of the viruses isolated from the patients were genetically related and formed an intrafamilial cluster of HIV-1 distinct from other subtype B viruses. Interindividual nucleotide variability in the C2-V3 and V4-C4-V5 domains ranged between 1.2 and 5.0% and between 2.2 and 7.5%, respectively, whereas divergence between HIV strains from the patients and control viral strains ranged from 6.6 to 29.3%. The amino acid signature patterns of viral clones from the three patients were closely related. In the C2-V3 region, two minor clones derived from the son's virus showed less nucleotide divergence (mean, 3.5 and 3.9%) than did the clones derived from the viruses of both parents or the seven other predominant clones derived from the virus from the son (mean, 5.4%). The top of the V3 loop of the last two clones and of all viral clones from the parents exhibited an unusual GPGG sequence. This is the first report of genotypic relatedness of HIV-1 in three adults of the same family in the absence of identified risk factor for transmission between the members of the family. Our findings suggest that atypical transmission of HIV may occur.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Ultrastructure of the retina in adult neuronal ceroid lipofuscinosis.

A 33-year-old woman died of biopsy-proven adult neuronal ceroid lipofuscinosis (NCL) or Kufs' disease marked by fingerprint and curvilinear lipopigments in neural and nonneural cell types. She had never experienced visual impairment or shown electroretinographic abnormalities. At autopsy, her retina appeared intact without degeneration at the light-microscopic level, but nerve cells in different layers were loaded with lipopigments of the granular type. This appears to be the third ultrastructural study of the retina in a patient with adult NCL, a former one showing preservation of the retina, another retinal degeneration. Thus, only further molecular genetic data will clarify the nosology of adult NCL with and without retinal degeneration.

Adult↗
PubMed1998

[Mechanisms underlying resistance of the bacteria responsible for nosocomial infections].

Resistance of nosocomial bacteria to antimicrobials is due to both natural and acquired factors. Production of inactivating enzymes (beta-lactamases, aminoglycoside detoxifying enzymes) is the most common mechanism in Gram-negative bacteria. The concomitant presence of other mechanisms such as abnormalities in the targets (for fluoroquinolones), permeability, or efflux of antimicrobials, explains why many nosocomial strains are resistant to multiple drugs. In Gram-positive bacteria, the main mechanism involves modifications in the bacterial targets of antimicrobials; for instance, changes in penicillin-binding proteins lead to penicillin resistance in enterococci and to methicillin resistance in staphylococci, whereas changes in peptidoglycans result in glycopeptide resistance in enterococci. As is the case for Gram-negative bacteria, the concomitant presence of other mechanisms is common, and as a result many nosocomial strains are multiresistant.

Acinetobacter↗
PubMed1997

Methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci: therapeutic realities and possibilities.

During the past decade much effort has been devoted worldwide to limiting the spread of methicillin-resistant Staphylococcus aureus. However, the recent emergence of almost untreatable vancomycin-resistant enterococci has led to a new and unexpected public health problem in hospitals and the community. Moreover, the threat of transfer of glycopeptide resistance to S aureus means that development of alternative antimicrobial strategies has become urgent. Whereas major advances have been made in our understanding of methicillin and vancomycin resistance mechanisms, we still need to identify the sources and reservoirs of the genetic determinants of resistance and to discover how they disseminate in the environment. The outcome of the battle between antimicrobials and bacteria is still uncertain, but the challenge is worth meeting.

Anti-Bacterial Agents↗
PubMed1997

A novel, double mutation in DNA gyrase A of Escherichia coli conferring resistance to quinolone antibiotics.

A spontaneous Escherichia coli mutant, named Q3, resistant to nalidixic acid was obtained from a previously described clinical isolate of E. coli, Q2, resistant to fluoroquinolones but susceptible to nalidixic acid (E. Cambau, F. Bordon, E. Collatz, and L. Gutmann, Antimicrob. Agents Chemother. 37:1247-1252, 1993). Q3 harbored the mutation Asp82Gly in addition to the Gly81Asp mutation of Q2. The different mutations leading to Gly81Asp, Asp82Gly, and Gly81AspAsp82Gly were introduced into the gyrA gene harbored on plasmid pJSW102, and the resulting plasmids were introduced into E. coli KNK453 (gyrAts) by transformation. The presence of Asp82Gly or Gly81Asp alone led to a low-level resistance to fluoroquinolones but not to nalidixic acid resistance. When both mutations were present, resistance to both nalidixic acid and fluoroquinolones was expressed. Purified gyrases of the different mutants showed similar rates of supercoiling. Dominance of the various gyrA mutant alleles harbored on plasmids was examined. The susceptibility to quinolones associated with wild-type gyrA was always dominant. The susceptibility to nalidixic acid expressed by the Gly81Asp mutant was dominant, while that expressed by the Asp82Gly mutant was recessive. From these results, we hypothesize that some amino acids within the quinolone resistance-determining region of gyrase A are more important for the association of subunits rather than for the activity of the holoenzyme.

Anti-Infective Agents↗
PubMed1997

Carbapenem resistance in a clinical isolate of Citrobacter freundii.

Carbapenem resistance was studied in two sets of Citrobacter freundii strains: (i) strain CFr950, resistant to imipenem (MIC, 16 microg/ml) and isolated in vivo during imipenem therapy, and strain CFr950-Rev, the spontaneous, imipenem-susceptible revertant of CFr950 selected in vitro, and (ii) strains CFr801 and CFr802, two imipenem-resistant mutants selected in vitro from the susceptible clinical isolate CFr800. In all strains, whether they were imipenem-susceptible or -resistant strains, production of the cephalosporinase was derepressed and their Km values for cephaloridine were in the range of 128 to 199 microM. No carbapenemase activity was detected in vitro. The role of cephalosporinase overproduction in the resistance was demonstrated after introduction of the ampD gene which decreased the level of production of cephalosporinase at least 250-fold and resulted in an 8- to 64-fold decrease in the MICs of the carbapenems. The role of reduced permeability in the resistance was suggested by the absence, in CFr950 and CFr802, of two outer membrane proteins (the 42- and 40-kDa putative porins whose levels were considerably decreased in CFr801) and the reappearance of the 42-kDa protein in imipenem-susceptible strain CFr950-Rev. This role was confirmed after introduction of the ompF gene of Escherichia coli into the CFr strains, which resulted in 8- to 16-fold decreases in the MICs of carbapenems for CFr802 and CFr950. We infer from these results that the association of reduced, porin-mediated permeability with high-level cephalosporinase production, observed previously in other gram-negative bacteria, may also confer carbapenem resistance on C. freundii.

Anti-Bacterial Agents↗
PubMed1997

Active efflux as a mechanism of resistance to ciprofloxacin in Streptococcus pneumoniae.

The accumulation of fluoroquinolones (FQs) was studied in a FQ-susceptible laboratory strain of Streptococcus pneumoniae (strain R6). Uptake of FQs was not saturable, was rapidly reversible, and appeared to occur by passive diffusion. In the presence of glucose, which energizes bacteria, the uptake of FQs decreased. Inhibitors of the proton motive force and ATP synthesis increased the uptake of FQs in previously energized bacteria. Similar results were observed with the various FQs tested and may be explained to be a consequence simply of the pH gradient that exists across the cytoplasmic membrane. From a clinical susceptible strain (strain SPn5907) we isolated in vitro on ciprofloxacin an FQ-resistant mutant (strain SPn5929) for which the MICs of hydrophilic molecules were greater than those of hydrophobic molecules, and the mutant was resistant to acriflavine, cetrimide, and ethidium bromide. Strain SPn5929 showed a significantly decreased uptake of ciprofloxacin, and its determinant of resistance to ciprofloxacin was transferred by transformation to susceptible laboratory strain R6 (strain R6tr5929). No mutations in the quinolone resistance-determining regions of the gyrA and parC genes were found. In the presence of arsenate or carbonyl cyanide m-chlorophenylhydrazone, the levels of uptake of ciprofloxacin by the two resistant strains, SPn5929 and R6tr5929, reached the levels of uptake of their susceptible parents. These results suggest an active efflux of ciprofloxacin in strain SPn5929.

4-Quinolones↗
PubMed1997

Presence of UDP-N-acetylmuramyl-hexapeptides and -heptapeptides in enterococci and staphylococci after treatment with ramoplanin, tunicamycin, or vancomycin.

Analyses of the peptidoglycan nucleotide precursor contents of enterococci and staphylococci treated with ramoplanin, tunicamycin, or vancomycin were carried out by high-pressure liquid chromatography coupled with mass spectrometry (MS). In all cases, a sharp increase in the UDP-N-actetylmuramoyl-pentapeptide or -pentadepsipeptide pool was observed. Concomitantly, new peptidoglycan nucleotide peptides of higher molecular masses with hexa- or heptapeptide moieties were identified: UDP-MurNAc-pentapeptide-Asp or pentadepsipeptide-Asp in enterococci and UDP-MurNAc-pentapeptide-Gly or -Ala and UDP-MurNAc-pentapeptide-Gly-Gly or -Ala-Gly in staphylococci. These new compounds are derivatives of normal UDP-MurNAc-pentapeptide or -pentadepsipeptide precursors with the extra amino acid(s) linked to the lysine epsilon-amino group as established by various analytical procedures (MS, MS-MS fragmentation, chemical analysis, and digestion with R39 D,D carboxypeptidase). Except for tunicamycin-treated cells, it was not possible to ascertain whether these unusual nucleotides were formed by direct addition of the amino acids to UDP-MurNAc-pentapeptide (or -pentadepsipeptide) or whether they arose by reverse reactions from lipid I intermediates to which the amino acids had been added.

Anti-Bacterial Agents↗
PubMed1997

Peptidoglycan structure of Lactobacillus casei, a species highly resistant to glycopeptide antibiotics.

The structure of the peptidoglycan of Lactobacillus casei ATCC 393, a species highly resistant to glycopeptide antibiotics, was examined. After digestion, 23 muropeptides were identified; monomers represented 44.7% of all muropeptides, with monomer tetrapeptides being the major ones. Fifty-nine percent of the peptidoglycan was O-acetylated. The cross-bridge between D-alanine and L-lysine consisted of one asparagine, although aspartate could be found in minor quantities. Since UDP-MurNAc-tetrapeptide-D-lactate is the normal cytoplasmic precursor found in this species, monomer tetrapeptide-lactate was expected to be found. However, such a monomer was found only after exposure to penicillin, suggesting that penicillin-sensitive D,D-carboxypeptidases were very active in normal growing cells.

Acetylation↗
PubMed1996

Peptidoglycan structure of Enterococcus faecium expressing vancomycin resistance of the VanB type.

Resistance to glycopeptide antibiotics in enterococci is due to the synthesis of UDP-MurNAc-tetrapeptide-D-lactate (where Mur is muramic acid) replacing the normal UDP-MurNAc-pentapeptide precursor. The peptidoglycan structures of an inducible VanB-type glycopeptide-resistant Enterococcus faecium, D366, and its constitutively resistant derivative, MT9, were determined. Using HPLC, 17 muropeptides were identified and were present regardless of whether resistance was expressed or not. The structures of 15 muropeptides were determined using MS and amino acid analysis. The cross-bridge between D-alanine and L-lysine consisted of one asparagine. No monomer pentapeptide or tetrapeptide-D-lactate could be identified. These results obtained with D366 (non-induced) and MT9 indicate that, in the absence of vancomycin, the cell wall synthetic machinery of E. faecium can process the lactate-containing precursor as efficiently as the normal pentapeptide. In contrast, the presence of subinhibitory inducing concentrations of vancomycin interfered with the synthesis of oligomers.

Amino Acid Sequence↗
PubMed1996

AAEM minimonograph #46: neurogenic muscle hypertrophy.

Muscle hypertrophy occurs uncommonly in several neurogenic disorders including neuropathies, radiculopathies, spinal muscular atrophy, and post-polio syndrome. Its pathogenesis varies in different circumstances. In the presence of generalized myokymia and neuromyotonia (Isaacs' syndrome), symmetrical hypertrophy appears to be the result of continuous spontaneous electrical stimulation of myofibers and, in some cases, results in type 1 myofiber preponderance. Focal hypertrophy occurring with radiculopathies and mononeuropathies was associated with complex repetitive discharges (CRDs) in approximately half the cases. CRDs may play a role in the pathogenesis of myofiber hypertrophy by continuous myofiber stimulation, but in some cases, with and without CRDs, myofiber hypertrophy may be related to mechanical events. Muscle enlargement seen in old polio appears to involve a significant degree of pseudohypertrophy, although some myofiber hypertrophy occurs. The symmetrical occurrence of hypertrophy in genetically determined disorders, such as spinal muscular atrophy, and hereditary motor and sensory neuropathy types 1 and 2 may have both a genetic and a mechanical basis in addition to pseudohypertrophy in some cases.

Humans↗
PubMed1996

Neuromyotonia and type I myofiber predominance in amyloidosis.

A case of amyloidosis presented with neurormyotonia and marked predominance of type I myofibers as documented by biopsy of an enlarged anterior tibialis muscle. This likely represents conversion of type II fibers to type I from continuous neuromyotonic stimulation. This transformation is well described to occur in animal models and this case represents a unique human example. Enlarged muscles likely reflected pseudohypertrophy.

Aged↗