[Moraxella catarrhalis: virulence and resistance mechanisms].

It is more than a century ago that Moraxella catarrhalis was discovered and described in some detail. However, it was not until the last decade that M. catarrhalis was recognized as a facultative pathogen, namely in otitis media (predominantly in children), sinusitis and nosocomial pneumonia in the group of elderly, debilitated patients.

Sulbactam and clavulanic acid: enzyme kinetics and synergy with ampicillin and mezlocillin.

The two beta-lactamase inhibitors, sulbactam and clavulanic acid, exhibit high affinity (K(I) < 10(-6)mol/l) for the beta-lactamases of Gram-negative organisms with predominantly penicillinase activity and much less affinity (especially clavulanic acid) for organisms with predominantly cephalosporinase activity. In tests to compare the synergy of these beta-lactamase inhibitors with other antibiotics, clavulanic acid and ampicillin or mezlocillin demonstrated greater synergy than sulbactam and ampicillin or mezlocillin, with isolates forming either a plasmid-coded beta-lactamase or a chromosomal enzyme with predominantly penicillinase activity. However, neither sulbactam nor clavulanic acid were able to protect ampicillin or mezlocillin adequately against inactivation by beta-lactamase overproducing variants of Klebsiella pneumoniae or Klebsiella oxytoca, irrespective of the extent of synergy seen with the corresponding wild strains.

Comparative evaluation of orally active antibiotics against community-acquired pathogens: results of eight European countries.

In this multicenter study conducted in eight European countries, 13,173 pathogens--all isolated from community-acquired infections in 1992 and 1993--were evaluated for their susceptibility to the following orally active antibiotics: penicillin G, ampicillin, amoxycillin plus clavulanic acid, cefaclor, cefuroxime, cefetamet, doxycycline and erythromycin. Ten centers in Italy, five in Germany, in the Netherlands and Switzerland, four in Greece and Spain, three in Hungary and one in Finland contributed to this study; ready-to-use standardized microtiter panels (Sceptor system, BBL, Heidelberg, Germany) were used throughout all assays. The most frequently encountered species were: Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae and non-typhoid Salmonella spp.

Comparative evaluation of orally active antibiotics against community-acquired pathogens: a multi-center study in five Mediterranean countries.

In 5 Mediterranean countries 7902 pathogens, all isolated in 1992 and 1993 from community-acquired infections, were studied for susceptibility to the following orally active antibiotics: penicillin G, ampicillin, ampicillin + sulbactam, amoxycillin + clavulanic acid (both 2:1 ratio), cefalexin, cefaclor, cefuroxime, cefetamet, doxycycline and erythromycin. Ten centers in Italy, 4 centers in Greece, 3 centers in Spain, and 1 center in Lebanon and Saudi Arabia contributed to this study; all centers used performed standardized microtiter panels (Sceptor, BBL, Heidelberg, FRG). The most frequently isolated pathogens were Escherichia coli (n = 1267), Proteus mirabilis (n = 843), Klebsiella pneumoniae (n = 771), enteric Salmonella spp.

[Multicenter evaluation of oral antibiotics: resistance behavior in 5 Swiss centers].

The susceptibility of 2196 fresh clinical isolates to twelve different oral compounds was assessed in five Swiss microbiology institutions during summer 1992. A standardized microdilution system including all other material necessary was employed to assess the antibacterial activity of penicillin G, ampicillin, ampicillin + sulbactam, amoxycillin + clavulanic acid, cefadroxil, cephalexin, cefaclor, cefuroxime, cefetamet, doxycycline, erythromycin and clindamycin. The aminopenicillins (including the beta-lactamase inhibitor combinations) were highly active against the streptococci, in combination with a beta-lactamase inhibitor they covered the majority of the bla+ E.

Antibacterial activity of oral antibiotics against anaerobic bacteria.

The spectrum and the antibacterial susceptibility of anaerobic bacteria to oral antibiotics isolated from clinical specimens was assessed in two different centres, the first receiving specimens from University departments and the second from general practitioners and small hospitals. Susceptibility was studied with a microtiter ready-to-use panel system, using the manufacturer's modified Wilkins-Chalgren's broth as the test medium for the following antibiotics: ampicillin, ampicillin+sulbactam, amoxicillin+clavulanic acid, cephalexin, cefaclor, cefuroxime, cefetamet, clindamycin, doxycycline and erythromycin. Anaerobic bacteria frequently encountered in clinical specimens from the University departments were mainly resistant Bacteroides spp.

[Sensitivity of penicillin-resistance pneumococci].

Fifty-three clinical Streptococcus pneumoniae isolates from Hungary and Spain which were either moderately susceptible to penicillin G (MIC 0.25-1 mg/l) or highly resistant (MIC > or = 2 mg/l) were studied for their antibacterial susceptibility to the following 14 agents: penicillin G, amoxicillin, mezlocillin, cefotaxime, ceftriaxone, amikacin, cotrimoxazole, erythromycin, rifampicin, vancomycin, fosfomycin, doxycycline, ciprofloxacin, and the dual-action compound Ro 23-9424. Rifampicin was the most active compound (MIC90 < or = 0.

Survey of antimicrobial resistance to oral antibiotics in Italy.

The susceptibility of approximately 4,200 fresh clinical isolates to eleven different orally available compounds was assessed in ten Italian microbiology institutions during summer 1991. A standardized microdilution system including all the material necessary was employed to assess the antibacterial activity of ampicillin, ampicillin plus sulbactam, amoxicillin plus clavulanic acid, cefadroxil, cephalexin, cefaclor, cefuroxime, cefetamet, doxycycline, erythromycin, and clindamycin. The amino-penicillins (including the beta-lactamase inhibitor combinations) were highly active against the streptococci, whereas cefetamet was the most active compound against Enterobacteriaceae, exhibiting good activity against the streptococci as well.

Importance of beta-lactamase stability in treating today's respiratory tract infections.

In respiratory tract infections Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae and Klebsiella spp. are the most frequently encountered bacterial pathogens. Resistance of clinical S.

Therapy of soft tissue infections with piperacillin/tazobactam.

The efficacy and safety of piperacillin in combination with the beta-lactamase inhibitor tazobactam were assessed in an open, multi-centre study of hospitalized patients with skin and soft tissue infections. A total of 136 patients from four countries were treated with piperacillin 4 g plus tazobactam 500 mg every 8 h. The mean duration of treatment was eight days.

Effects of cefaclor, cefetamet and Ro 40-6890 on inflammatory responses of human granulocytes.

The effect of three cephalosporins (cefetamet, cefaclor and Ro 40-6890) upon human granulocytes and their ability to modulate the chemiluminescence response, phagocytose, kill bacteria and generate leukotrienes was studied. In the presence of the cephalosporins there was a significant increase in phagocytosis of Escherichia coli. The bactericidal activity of human granulocytes for several other bacteria was also enhanced.

Cefetamet pivoxil: a review of its microbiology, toxicology, pharmacokinetics and clinical efficacy.

Cefetamet pivoxil is an oral, third-generation cephalosporin whose broad spectrum of antibacterial activity and favorable pharmacokinetic profile make it particularly suitable for the treatment of a wide range of infectious diseases. Cefetamet has high in vitro activity against both gram-positive and gram-negative bacteria that cause a number of respiratory tract and urinary tract infections. These include penicillin-sensitive Streptococcus pneumoniae, Streptococcus spp, Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli, Proteus spp.

Lipopolysaccharide alterations responsible for combined quinolone and beta-lactam resistance in Pseudomonas aeruginosa.

Resistant variants of three clinical Pseudomonas aeruginosa isolates were obtained in the presence of aztreonam. The variants exhibited a four- to eightfold increase in the minimal inhibitory concentrations to beta-lactam antibiotics (except imipenem) to quinolones, such as norfloxacin and fleroxacin, chloramphenicol and tetracycline, but not to gentamicin and polymyxin B. beta-Lactamase production was barely detectable in both wild-type strains and the resistant clones.

The threat of resistance to the new oral cephalosporins.

Phenotypic resistance to beta-lactam antibiotics is mainly due to the prevalence of beta-lactamases. The most common enzymes responsible for resistance to aminopenicillins and older (1st generation) cephalosporins are the TEM-1, TEM-2, OXA-1 and SHV-1 enzymes, all of which are plasmid-mediated. The recent development of oral cephalosporins sharing structural features and an antimicrobial spectrum comparable to that of 3rd-generation cephalosporins has provided highly active compounds for the management of outpatient infections.

Influence of exogenous factors and antibiotics on the cytoplasmic membrane proteins of Staphylococcus aureus.

The influence of various nutrient media, growth temperature, phase of growth and subinhibitory concentrations of antibiotics from various groups on the cytoplasmic membrane proteins was studied in 6 clinical S. aureus isolates; further study included the comparison of the cytoplasmic membrane proteins in antibiotic-sensitive wild-type (parent) strains with their resistant counterparts. Resistant clones could be selected with a frequency ranging from 10(-7) to 10(-8) from the parent strain at twice the MIC.

Beta-lactamase inhibitors: relation between kinetic data and in-vitro synergism studies.

Because of the need for control of beta-lactamase-mediated resistance and the recent development of tazobactam, the author has examined the inhibitors of various beta-lactamases for their effectiveness. On the basis of the kinetic data, tazobactam exhibited the highest affinity to various beta-lactamases. A combination with tazobactam was found to enhance the effectiveness of piperacillin against S.

[Effect of cyclic nucleotides on beta-lactamase production and outer membrane proteins of clinical Xanthomonas maltophilia isolates].

Resistance of clinical Xanthomonas maltophilia isolates to beta-lactam compounds is influenced considerably by the nutrient medium employed for sensitivity testing; the organisms were much more resistant to beta-lactams when susceptibility testing was performed in Mueller-Hinton broth as compared to Isosensitest broth as the nutrient medium. Consequently, the influence of cyclic nucleotides was studied on beta-lactamase expression and outer membrane proteins in more detail. The exogenous supply of 5 mmol/l c-AMP or its lipophilic derivative c-AMP-N6,O2-dioctanoyl resulted in a marked reduction of enzyme production as compared to the control assay; 0.

Carbapenem resistance in Enterobacter aerogenes is due to lipopolysaccharide alterations.

The extensive characterization of 2 clinical Enterobacter aerogenes isolates resistant to all beta-lactam antibiotics including imipenem revealed that imipenem resistance could not be attributed to overproduction of the chromosomal beta-lactamase; moreover, it was lost after subcultivation and can be thus considered as unstable. The comparison of sensitive and resistant clones revealed that the beta-lactamase in the resistant clones was less inducible in the resistant clones and moreover, there was an altered 2-keto-3-deoxyoctonate/carbohydrate ratio in the resistant clones as compared to the imipenem-sensitive clones, thus suggesting alterations in the lipopolysaccharide (LPS). Neither enzymatic degradation of both imipenem and meropenem nor alterations of the outer membrane proteins could be observed.

Antibiotic susceptibility and outer membrane proteins of clinical Xanthomonas maltophilia isolates.

Twenty clinical Xanthomonas maltophilia isolates were studied for their susceptibility to various antibiotics and for their outer membrane protein profiles and compared to Pseudomonas aeruginosa isolates. Among the antibiotics studied, fleroxacin and ciprofloxacin exhibited the greatest activity (MIC90 4 micrograms/ml). All the X.

Imipenem resistance in Acinetobacter baumanii is due to altered penicillin-binding proteins.

The comparison of a clinical Acinetobacter baumanii isolate (strain No. 4852/88) and its selected imipenem-resistant (IMR) clone exhibited a complex reorganization of the penicillin-binding proteins (PBPs) with diminished labelling of all PBPs except the 24-kD PBP which showed an increased binding of 14C-penicillin. This protein could not be saturated by preincubation of membranes with imipenem at 8-fold the MIC of imipenem, thus indicating PBP alterations responsible for imipenem resistance.

Cefpodoxime: comparable evaluation with other orally available cephalosporins. With a note on the role of beta-lactamases.

The antibacterial activity of cefpodoxime, a new orally active methoxy-imino cephalosporin was evaluated in 470 recent isolates of gram-positive cocci and gram-negative rods from clinical specimens and compared to that of other orally active beta-lactam compounds. Cefpodoxime was highly active against ampicillin-resistant enterobacteria producing the plasmid-mediated TEM-1, TEM-2 or OXA-1 enzymes, as was the case for the other newer compounds. However, it was poorly active against cefuroxime-resistant (MIC greater than or equal to 16 mg/l) E.

[Causes of quinolone resistance in gram-negative bacteria].

Some years ago the 6 alpha-fluoroquinolones were introduced into therapy; within the recent years the frequency of quinolone-resistant enterobacteria remained unchanged at a very low level. The frequency of resistant Staphylococcus aureus isolates in clinical specimens increased slowly and there was a markedly increase in quinolone-resistant Pseudomonas aeruginosa isolates. So far, resistance to quinolones among gram-positive organisms can be attributed to alterations of the subunit A of the DNA-gyrase, whereas in gram-negative rods both alterations of the subunits A and B of the DNA-gyrase as well as alterations of the composition of the outer membrane can be made responsible for phenotypic resistance.

Heterogeneity of beta-lactamase production in Pseudomonas maltophilia, a nosocomial pathogen.

Twenty Pseudomonas maltophilia isolates were examined for susceptibility to beta-lactam antibiotics, including carbapenems, and for beta-lactamase production. All the isolates were resistant to imipenem (MICs 64-512 mg/l) and to a lesser extent, to meropenem (MICs 16-256 mg/l). None of the isolates produced significant amounts of beta-lactamase without induction.