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PubMed1987

Frequencies of variants resistant to different aminoglycosides in Pseudomonas aeruginosa.

The MICs of aminoglycosides for Pseudomonas aeruginosa are higher than those for Enterobacteriaceae and the number of variants resistant to high concentrations of aminoglycosides is greater in P. aeruginosa than in Escherichia coli. However, when the frequencies of resistant variants at different multiples of the MIC were calculated, these frequencies were similar in P. aeruginosa and E. coli. When large inocula of strains of P. aeruginosa, which were classified as sensitive in conventional MIC determinations, were incubated with amikacin, gentamicin, netilmicin or tobramycin at the break-point concentrations between sensitivity and resistance, 82%, 90%, 90% and 15%, respectively, of the strains regrew. The corresponding percentages for Enterobacteriaceae were much lower. The clinical relevance of this pronounced regrowth of P. aeruginosa is discussed.

Aminoglycosides↗
PubMed1987

Aminoglycoside resistance patterns in clinical isolates of Enterobacteriaceae from Czechoslovakia.

Multi-resistant Enterobacteriaceae isolated mainly from urine specimens from patients at the Department of Urology, Kramáre Hospital, Bratislava, were characterized for resistance phenotype. Seventeen gentamicin-resistant isolates were further studied for the presence of aminoglycoside-modifying enzymes. Five enzymes were detected: AAC(2'), AAC(3)-II, AAC non-characterized, ANT(2") and APH(3')-I. The substrate range of these enzymes was found to correlate with the resistance phenotype in most isolates. In our collection the AAC(3)-II enzyme that inactivates gentamicin, sisomicin, tobramycin and netilmicin was predominant. Predominance of this type of modifying enzyme has been observed also in resistant Gram-negative strains in Belgium, The Netherlands and Chile, in contrast to the United States, Federal Republic of Germany, Switzerland, Greece and Turkey, where ANT(2") has been the most common enzyme.

Acetyltransferases↗
PubMed1987

Influence of various antibiotics on phagocytosis of Staphylococcus aureus by human polymorphonuclear leucocytes.

The influence of several new antibiotics on phagocytosis of two strains of Staphylococcus aureus by human polymorphonuclear leucocytes was studied with a radioisotopic method. The following antibiotics were tested in concentrations obtained in the serum after standard administration: gentamicin, netilmicin, amikacin, oxacillin, clindamycin, vancomycin, teicoplanin, rifampicin, ansamycin, coumermycin, enoxacin, ciprofloxacin, two new fluoro-quinolones CI 934 and RO 236240, and LY 146032 a new lipopeptidic antibiotic. Among them, only coumermycin significantly decreased phagocytosis, this was dependent on concentration, strain and source of the polymorphonuclear leucocytes.

Aminocoumarins↗
PubMed1987

AAC(1): a new aminoglycoside-acetylating enzyme modifying the Cl aminogroup of apramycin.

An aminoglycoside-acetylating enzyme produced by a strain of Escherichia coli with an unusual resistance phenotype was characterized. This enzyme was found to mono-acetylate apramycin, butirosin, lividomycin and paromomycin and diacetylate ribostamycin and neomycin to give reaction products which were distinguishable by HPLC analysis from those of AAC(2'), AAC(3) and AAC(6') enzymes. The enzyme, however, was not found to acetylate amikacin, fortimicin, geneticin, gentamicin, kanamycin A, netilmicin or tobramycin. The reaction product from the action of this enzyme on apramycin was purified and identified by nuclear magnetic resonance studies as 1-N-acetyl apramycin. The second site at which ribostamycin and neomycin B were modified by this enzyme was not determined but is postulated as the 6'-amino group. It is proposed that this enzyme be named AAC(1).

Acetyltransferases↗
PubMed1988

Susceptibility of Pseudomonas pseudomallei to new beta-lactam and aminoglycoside antibiotics.

Pseudomonas pseudomallei is resistant to many antimicrobial agents. We determined the susceptibility to twelve beta-lactams and six aminoglycosides of twelve isolates of P. pseudomallei. Imipenem (MIC range 0.5-1.0 mg/l; MIC90 1.0 mg/l), ceftazidime (MIC range 1-8 mg/l; MIC90 8.0 mg/l), amoxycillin/clavulanate (MIC range 4-8 mg/l; MIC90 8.0 mg/l), piperacillin (MIC range 4-16 mg/l; MIC90 8.0 mg/l), and carumonam (MIC range 4-16 mg/l; MIC90 8.0 mg/l) were the most active. Aminoglycosides were relatively inactive, for example, gentamicin (MIC range 16-64 mg/l; MIC90 64 mg/l), netilmicin (MIC range 16-128 mg/l; MIC90 128 mg/l) and amikacin (MIC range 32-64 mg/l; MIC90 64 mg/l).

Aminoglycosides↗
PubMed1988

Susceptibility of Hong Kong isolates of methicillin-resistant Staphylococcus aureus to antimicrobial agents.

Two hundred and sixty-six non-replicate Hong Kong isolates of methicillin-resistant Staphylococcus aureus were tested for their susceptibility to various anti-staphylococcal agents. Multiple resistance was common. More than 95% of patient isolates were resistant to both gentamicin and tetracycline, 68% to erythromycin, 37% to chloramphenicol, 10% to trimethoprim, 5% to rifampicin and 2% to fusidic acid. No isolate was resistant to all these agents, but nineteen different patterns of resistance were identified. Selected gentamicin-resistant isolates were tested against other aminoglycosides, and were sensitive to amikacin and netilmicin. The pattern of aminoglycoside resistance indicated that all isolates produced the aminoglycoside-modifying enzymes APH-(2") and AAC-(6')-I. All isolates were sensitive to vancomycin and teicoplanin. A single strain was resistant to three of the five quinolones tested, but resistance to all the quinolones could be induced easily in vitro by exposure to increasing subinhibitory concentrations of norfloxacin in broth.

Anti-Bacterial Agents↗
PubMed1988

Comparative study on antagonistic effects of low pH and cation supplementation on in-vitro activity of quinolones and aminoglycosides against Pseudomonas aeruginosa.

The antagonistic effects of physiological levels of Ca++ and Mg++ on the in-vitro activity of aminoglycosides and quinolones against Pseudomonas aeruginosa were studied at both pH 7.4 and 5.5. Adding Mg++ and Ca++ (100 mg/l) to commercial media deficient of these cations increased the MICs and MBCs of ciprofloxacin and enoxacin four-fold (2 P less than 0.01), which was significantly less than the 16-fold increase found for gentamicin and netilmicin (2 P less than 0.01). However, the activity of both aminoglycosides and quinolones was similarly affected by reducing the pH to 5.5 (giving eight-fold increases in MICs) or by the combination of both low pH plus cation supplementation (giving 16-fold increases in MICs). These data raise the question whether antagonizing factors should be considered not only for aminoglycosides, but also for quinolones during routine susceptibility tests on P. aeruginosa.

4-Quinolones↗
PubMed1988

Postantibiotic effect of aminoglycosides on gram-negative bacteria evaluated by a new method.

The in-vitro postantibiotic effect (PAE) of amikacin, gentamicin, netilmicin and tobramycin was investigated by a bioluminescent assay of bacterial ATP. Two strains each of Escherichia coli and Pseudomonas aeruginosa were exposed for 1 h to different concentrations of the aminoglycosides. The aminoglycoside was removed by a 10(-3) dilution, and regrowth of bacteria was followed at hourly intervals by monitoring bacterial ATP. This method simplified the PAE studies and made such studies possible at high aminoglycoside concentrations. The length of the PAE was dose-dependent for all the aminoglycosides studied. The PAEs ranged between three and seven hours for all four strains at the aminoglycoside concentrations normally reached in serum during standard dosing. The long PAE of aminoglycosides, especially after exposure to high drug concentrations, constitutes an argument in favour of administering aminoglycosides in higher-than-usual doses with longer intervals between doses. This proposal is also supported by recent pharmacokinetic, bacteriological and toxicity data.

Adenosine Triphosphate↗
PubMed1988

Intraphagocytic penetration of antibiotics.

The penetration of several antibiotics into human polymorphonuclear leucocytes was measured with a bioassay. The aminoglycosides (gentamicin, netilmicin), oxacillin and LY146032, a new lipopeptidic antibiotic, had a penetration which was generally less than 60%, whereas new fluoro-quinolones (enoxacin, ciprofloxacin, CI934, Ro236240) and rifamycins (rifampicin, LM427) were concentrated 2.4 to 14.2-fold. The concentration of vancomycin and teicoplanin associated with the neutrophils appeared to be saturable over the range of extracellular concentrations tested (5-20 mg/l). Coumermycin, an inhibitor of DNA-gyrase, was highly concentrated (11.3 to 16.6-fold) within the neutrophils. The penetration of clindamycin and erythromycin was low (0.60- to 1.48-fold).

4-Quinolones↗
PubMed1988

Resistance of bacterial pathogens to four aminoglycosides and six other antibacterials and prevalence of aminoglycoside modifying enzymes, in 20 UK centres.

A total of 5116 non-fastidious bacterial strains isolated from either blood or urine culture were collected from 20 geographically distributed centres within the UK. Upon receipt the strains were identified and the minimum inhibitory concentrations of ten antimicrobial agents in hospital usage were determined for each of the strains. All laboratories submitted a similar range of bacterial species and in species normally considered as sensitive the overall rates of resistance to the different antibiotics tested were: amikacin 2.4%, gentamicin 3.7%, netilmicin 2.6%, tobramycin 3.4%, ampicillin 41.7%, cefadroxil 11.6%, cefotaxime 1.4% [corrected], cefuroxime 4.3%, ciprofloxacin 0.6% and trimethoprim 13.0%. For those strains resistant to one or more aminoglycosides the mechanisms of resistance responsible were determined from the aminoglycoside-resistance patterns of the strains to 16 different aminoglycoside antibiotics. The predominant mechanisms of resistance found were APH(2") + AAC(6') production in staphylococci. AAC(2') production in Providencia spp., and AAC(3) production in the other Gram-negative genera.

Aminoglycosides↗
PubMed1988

In-vitro activity of seventeen antimicrobial compounds against seven species of mycobacteria.

Within attainable serum concentrations, quinolones, especially ciprofloxacin, inhibited strains of Mycobacterium tuberculosis, M. xenopi, M. kansasii, M. fortuitum and M. marinum; vancomycin inhibited M. tuberculosis, the M. avium-intracellulare-scrofulaceum complex. M. kansasii, M. xenopi and M. chelonei; erythromycin was active against M. kansasii, M. xenopi and M. fortuitum, minocycline against M. kansasii and M. marinum and netilmicin and cefuroxime against M. xenopi. Aztreonam showed some activity against M. tuberculosis but little or no effect was shown by five cephalosporins or imipenem.

Anti-Bacterial Agents↗
PubMed1990

Enhancement of leucocyte killing of resistant bacteria selected during exposure to aminoglycosides or quinolones.

In vitro exposure to aminoglycosides and quinolones may select resistant subpopulations, although this is not a common clinical problem. This study was designed to determine whether aminoglycoside and quinolone resistant bacteria are more susceptible to leucocyte (WBC) killing. Cultures of Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus were pretreated with aminoglycosides (netilmicin, amikacin) and quinolones (enoxacin, ciprofloxacin) at 1/2 MIC for 24 h. The median susceptibility of bacteria selected during antibiotic exposure was reduced four-fold. These resistant subpopulations (10(6) cfu/ml) were exposed to 10(7) human WBC/ml for 6 h in antibiotic free cell culture media with 10% fresh human serum. Enhanced WBC activity was observed against all antibiotic pretreated bacteria in comparison with untreated controls (P less than 0.01). After 4 h of exposure to WBC, aminoglycoside or quinolone pretreated cultures of P. aeruginosa were reduced by 1.3-1.7 log, in comparison with a reduction of only 0.5 log in control cultures. These observations may explain in part the infrequent therapeutic failure with these drugs in hosts with competent neutrophils despite the potential of these drugs to select resistant strains in vitro.

4-Quinolones↗
PubMed1990

Resistance to aminoglycoside antibiotics in gram-negative bacilli and staphylococci isolated from blood. Report from a European collaborative study. The ESGAR Study Group (European Study Group on Antibiotic Resistance).

The incidence of resistance to gentamicin, tobramycin, amikacin and netilmicin was determined by the microdilution method in Mueller-Hinton broth among blood culture isolates consecutively collected in 37 laboratories in 14 European countries. The distribution of bacteria was similar in each laboratory, Escherichia coli and staphylococci predominating. Resistance levels varied between laboratories but they were higher to all four antibiotics in Southern Europe than in Central and Northern Europe. Aminoglycoside resistance was usually associated with production of aminoglycoside-modifying enzymes, ANT(2"), AAC (3)-V, AAC (6')-I predominating in Gram-negative bacilli and APH (2") + AAC (6') and ANT (4')-I in staphylococci.

Aminoglycosides↗
PubMed1990

Resistance mechanisms of multiresistant serotype 012 Pseudomonas aeruginosa isolated in Europe.

Serotype 012 Pseudomonas aeruginosa resistant to gentamicin (MIC greater than 4 mg/l) and carbenicillin (MIC greater than 128 mg/l) occur widely in Europe and are homogeneous in their phenotypic and genetic properties. It has been suggested that a single multiresistant strain of this serotype has become widespread. This study examined the resistance mechanisms present in multiresistant serotype 012 P. aeruginosa isolates from Austria, Belgium, France, Greece, Italy, Holland, West Germany and the UK. Disseminated isolates produced a PSE-1 type beta-lactamase, correlating with their resistance to the known substrates of this enzyme (carbenicillin, azlocillin and cefsulodin). These isolates also reacted with gene probes for the aminoglycoside modifying enzymes AAC(6')I and ANT(3'). The probe for AAC(6')I is known to cross-react with the gene for AAC(6')II. The fact that the organisms were resistant to netilmicin, gentamicin, sisomicin and tobramycin, but less so to amikacin, suggested that the latter enzyme was produced rather than AAC(6')I. PSE-1 beta-lactamase and the gene for AAC(6')I/AAC(6')II were absent from the International Antigenic Typing Scheme 012 reference strain, which was sensitive to beta-lactams and aminoglycosides, and also from a multiresistant serotype 012 strain isolated at a London burns unit in 1987. These organisms have been shown previously to be distinct from the disseminated multiresistant strain in their phenotypic properties. Two 012 isolates appeared to have additional resistance determinants to amikacin and isepamicin.

Aminoglycosides↗
PubMed1992

Maintenance requirements of Escherichia coli ATCC 25922 in the presence of sub-inhibitory concentrations of various antibiotics.

Escherichia coli ATCC 25922 was grown in minimal medium M63, with glucose 0.1 gL as limiting energy substrate, in the presence of sub-inhibitory concentrations of netilmicin, habekacin, tobramycin, dibekacin, amikacin, kanamycin, amoxycillin, ampicillin, cephalothin, cefoxitin and nalidixic acid. Maintenance requirements were determined with a simple relationship derived from batch growth curves. The apparent relationship between maintenance requirements and antibiotic concentration is an exponential increase, log m(c) = log mo + k.c, where m is maintenance, c antibiotics concentration, mo maintenance without antibiotics, and k a constant. Values for k were found to be in the range 0.5-2.0 mg-1.L.

Amikacin↗
PubMed1992

In-vitro antimicrobial susceptibility of Rhodococcus equi.

Rhodococcus equi is an intracellular facultative, Gram-positive cocco-bacillary organism of increasing importance as a pulmonary pathogen in HIV-positive patients. This study was carried out to evaluate the optimal antibiotic combinations for treating such infections. Four human R. equi isolates and one reference strain were tested for their susceptibilities to 36 antibiotics. In-vitro the most active antibiotics were amikacin, gentamicin, netilmicin, erythromycin, clarithromycin, roxithromycin, ciprofloxacin, sparfloxacin, rifampicin, vancomycin, teicoplanin, doxycycline, minocycline, imipenem, meropenem and trimethoprim/sulphamethoxazole. The only bactericidal antibiotics were the aminoglycosides, ciprofloxacin, sparfloxacin and vancomycin. As determined by FIC indices, four combinations were synergistic: rifampicin-erythromycin, rifampicin-minocycline, erythromycin-minocycline and imipenem-amikacin. However, no antibiotic combinations were synergistic with the time-kill kinetic method at achievable serum concentrations or at ten-fold and half-fold the MICs. Frequencies of selection of antibiotic-resistant mutants determined at concentrations of five- and ten-fold the MICs ranged from less than 1 x 10(-8) for erythromycin and trimethoprim/sulphamethoxazole to 5 x 10(-4) for amikacin. These results may be of help in selecting the antibiotics for treating infected HIV-positive patients.

Anti-Bacterial Agents↗
PubMed1992

Rapid increase in the prevalence of high-level aminoglycoside resistance among enterococci isolated from blood cultures during 1989-1991.

At St Elizabeth Hospital Medical Center in Youngstown, Ohio, USA, the first blood culture isolate of Enterococcus faecalis with high-level gentamicin resistance (MIC > 2000 mg/L) was seen in 1985, and the prevalence of high-level gentamicin resistance among enterococci isolated from blood cultures during 1985-8 was 9%. During the period 1989-91, the prevalence of high-level gentamicin resistance among enterococci isolated from blood cultures increased to 35% (44 of 126 strains). Increases in the prevalence of high-level resistance to amikacin, tobramycin, netilmicin, kanamycin and streptomycin were also demonstrated. Ten of 44 strains (23%) with high-level gentamicin resistance did not exhibit high-level resistance to streptomycin. Of the 126 strains of enterococci, 52% had high-level resistance to at least one aminoglycoside.

Aminoglycosides↗
PubMed1992

Frequencies of subpopulations of aminoglycoside- and vancomycin-resistant variants in Staphylococcus aureus and Staphylococcus epidermidis.

Selection and regrowth of resistant variants, which are present in low frequencies in the initial inoculum, were seen when large inocula of five strains of Staphylococcus aureus and four strains of Staphylococcus epidermidis were incubated in broth with amikacin, gentamicin, netilmicin and tobramycin. Statistical analysis showed no significant difference between the aminoglycosides in the selective growth of resistant variants (P > 0.5). Vancomycin differed significantly from the aminoglycosides in both the frequency of, and selection of resistant variants (P < 0.001). No bacteria resistant to > 1 x MIC was seen in the vancomycin-exposed cultures of S. aureus and S. epidermidis, while in most aminoglycoside-exposed cultures, bacteria resistant to 4-16 x MIC were seen.

Aminoglycosides↗