Novel plasmid-mediated ceftazidimase from Klebsiella pneumoniae isolates.
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Ceftazidime↗
Biomedical subjects
D Sirot
Publications and source records attributed to D Sirot.
[In vitro antibacterial activity of apalcillin on aerobic bacteria and the regression curve].
Minimal inhibitory concentrations (MICs) of apalcillin (APL) were evaluated by agar dilution on 1,201 bacterial strains isolated simultaneously in four university hospitals; agar diffusion tests (disks APL: 75 micrograms) were performed on these strains to establish relationship between MIC and zone diameters. For Enterobacteriaceae naturally non beta-lactamase-producing (E. coli and P. mirabilis), mode MIC was 0.5 microgram/ml; some acquired penicillinase-producing strains were only inhibited by concentrations greater than or equal to 16. Chromosomal penicillinase producing Klebsiella were inhibited by 2 to 8 micrograms/ml but APL was inactive on acquired penicillinase-producing strains. For chromosomal cephalosporinase-producing species (Enterobacter, Citrobacter, Serratia, indole + Proteus and Providencia) two populations of strains were observed: one sensitive and the second resistant to carboxypenicillins: on the first population, mode MIC of APL was 1 to 4 micrograms/ml; on the second MIC were generally greater than or equal to 64 micrograms/ml. P. aeruginosa strains sensitive to carboxypenicillins were inhibited by 1 and 2 micrograms/ml; this activity was diminished on strains resistant to these antibiotics (MIC APL 8-32). MIC of Acinetobacter varied to 0.25 to greater than 128 with a majority of strains inhibited by 4 to 64 micrograms/ml. APL was active against non penicillinase producing Staphylococci; mode MIC was 2 micrograms/ml for Enterococci. Correlation coefficient of regression curve was 0.87. For critical concentrations less than or equal to 8 and greater than 64 micrograms/ml, critical diameters could be greater than or equal to 19 and less than 12 mm.
Acinetobacter↗
The kinetics of SHV-2 plasmid-mediated beta-lactamase compared to those of the parent enzyme from which it is derived.
Kinetic constants were determined for two closely related plasmid-mediated beta-lactamases: SHV-2 and PIT-2 (also known as SHV-1). These enzymes were synthesized constitutively. They were highly sensitive to the action of the inhibitors clavulanic acid and sulbactam, and they lacked activity against cephamycins and also imipenem. Both enzymes were significantly active against penicillins and first-generation cephalosporins, and the main difference concerned the third-generation cephalosporins: SHV-2 was highly active against these compounds whereas PIT-2 was not.
Anti-Bacterial Agents↗
Transferable resistance to third-generation cephalosporins in clinical isolates of Klebsiella pneumoniae: identification of CTX-1, a novel beta-lactamase.
Approximately 10% (89 isolates) of Klebsiella pneumoniae isolated in 1985 from patients in intensive care units in Clermont-Ferrand exhibited a complex resistance phenotype towards antibiotics. They were resistant to amino-, carboxy- and ureidopenicillins, aminoglycosides (except gentamicin), chloramphenicol, sulphonamides, tetracyclines and, most importantly, to cephalosporins (except cefoxitin and latamoxef) and to aztreonam. The metabolic profile of fifty isolates was identical and seven were selected for further study. All the resistance characters in these isolates were transferable to Escherichia coli by conjugation and were lost en bloc after treatment with ethidium bromide. Agarose gel electrophoresis of crude lysates of the wild types and their transconjugants indicated that the multiple resistances were mediated by a 95kb plasmid, pCF04. The seven isolates selected for study and their corresponding transconjugants, constitutively produced a plasmid-mediated beta-lactamase with a pI of 6.3 that was much more active against third-generation cephalosporins than against cephalothin. The substrate profile and the isoelectric-focusing behaviour of this enzyme differed from those of other known plasmid-mediated beta-lactamases, and the enzyme was designated CTX-1. A chromosomally-encoded SHV-1 (PIT-2) penicillinase (pI 7.7) was also present in the seven K. pneumoniae isolates but did not transfer. Resistance to aminoglycosides in the K. pneumoniae isolates was due to synthesis of a 6'-aminoglycoside acetyltransferase type IV. Our data indicate an epidemic of antibiotic multiply-resistant strains of K. pneumoniae producing a new beta-lactamase.
Cephalosporins↗
Spread of SHV-1 beta-lactamase in Escherichia coli isolated from fecal samples in Africa.
Ninety-seven (42%) Escherichia coli strains isolated in Senegal from fecal samples produced beta-lactamases. Among them, 29 (30%) isolates produced SHV-1 beta-lactamase that was plasmid mediated. The plasmids belonged to four incompatibility groups. Various degrees of TEM-1 expression in the presence of SHV-1 were observed.
Escherichia coli↗
[In vitro effect of piperacillin on aerobic bacteria. Variations according to the phenotypes of resistance to beta-lactam antibiotics].
In a first study the MICs of piperacillin (PIP), mezlocillin (MEZ), azlocillin (AZL), carbenicillin (CARB) and ticarcillin (TIC) against 563 strains of aerobic bacteria were compared. The MIC50 of PIP against E. coli and P. mirabilis was 0.5 to 1 mg/l, that is equal to those of MEZ and TIC but 2 or 3 times lower than those of AZL and CAR. The MIC50 of PIP and MEZ against Klebsiella, a species that is naturally resistant to TIC and CAR, was 4 mg/l. Enterobacter, Serratia and Citrobacter showed two populations of strains: the first was sensitive to the five penicillins tested (MIC50 of PIP: 1 to 2 mg/l); the second was resistant to all of them. PIP and AZL were more active (MIC50 8 mg/l) against Ps. aeruginosa than MEZ, TIC and CAR. All five penicillins had limited activity against Acinetobacter (MIC50 less than 16 mg/l). PIP, MEZ and AZL were more active than TIC and CAR against enterococci. In a second study, the activity of PIP was evaluated by standard sensitivity tests on 4993 strains of enterobacteria, Ps. aeruginosa and Acinetobacter classified according to their phenotype of resistance to beta-lactam antibiotics. PIP was regularly active against enterobacteria and Ps. aeruginosa strains devoid of acquired resistance. The activity of PIP was significantly reduced against enterobacteria strains with a phenotype suggesting induced penicillinase production. However, the inhibition zone diameters, although reduced, remained within what is now considered the sensitivity range (notably with E. coli and Proteus spp), which raises the problem of in vitro tests interpretation. PIP was active against E. coli strains with a "cephalosporinase" phenotype, but inactive against cefotaxime resistant strains of: Enterobacter, Citrobacter and Serratia. The activity of PIP on CAR-resistant Ps. aeruginosa strains was significantly reduced, but the inhibition zone diameter in one quarter of them was still within limits of sensitivity.
Azlocillin↗
[In vitro comparative study of piperacillin-aminoglycosides combinations against Enterococci and Enterobacteriaceae].
The hundred and ninety-two combinations were tested against 17 strains chosen from the results of MIC determination (disc method): 5 enterococci exhibiting low level resistance (r) or high level resistance (R) to streptomycin (S) and gentamicin (G): 2 strains Sr Gr, 2 strains SR Gr and 1 strain Sr GR; 12 enterobacteria chosen for their resistance phenotypes to beta-lactams and aminoglycosides and because they are the most frequent clinical isolates: 2 strains Amos Tics Ctns (group 1), 4 strains AmoR Tics CtnR (gr. II), 4 strains AmoR TicR Ctns (gr. III) and 2 strains AmoR TicR CtnR (gr. IV). MIC and MBC were assessed for the 17 strains (Mueller Hinton broth). Combinations were carried out by a checkerboard micromethod. FBC index was calculated for each combination. Against enterococci the 50 combinations were: piperacillin versus ampicillin + aminoglycosides (streptomycin, tobramycin, amikacin, gentamicin, netilmicin). Against enterobacteria piperacillin was combined with different aminoglycosides depending on their resistance phenotypes. These combinations were compared with ticarcillin or mezlocillin or cefotaxime + aminoglycosides (total number 142). The species studied produced different results: with the enterococci Gr synergistic effects (FBC = 0.62-0.75) were rare; additive and indifferent effects were predominant. With the GR strain some antagonistic effects were observed. With the enterobacteria, in groups I and II synergistic effects were frequent and almost equivalent regardless of the beta-lactam chosen. In groups III and IV (TicR) piperacillin MICs were greater than or equal to 128 mg/l and mezlocillin MICs greater than 512 mg/l; the synergistic effects were significant (FBC from 0.25 to 0.62). beta-lactam + amikacin or netilmicin, and especially piperacillin + amikacin, were found to have the most frequent synergistic effects upon the strains tested. Mezlocillin combinations cannot be used clinically; the use of piperacillin combinations requires further discussion. On the other hand, cefotaxime + aminoglycosides combinations are active against those TicR strains.
Aminoglycosides↗
A comparison of agar dilution, identification of beta-lactamases and disc diffusion methods for assessing the sensitivity to ticarcillin-clavulanic acid.
The in-vitro antibacterial activity of Timentin has been evaluated with a view to proposing valid criteria for sensitivity and resistance. Minimal inhibitory concentrations (MIC) were determined for 284 strains including Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter spp., staphylococci and enterococci. The same strains were also used for the determination of inhibition zones around discs containing 75 micrograms ticarcillin and 10 micrograms clavulanic acid, and a straight regression line was drawn correlating MIC with inhibition zones. The bacterial population was subsequently grouped according to the diameters of inhibition zones of the antibiogram for 2427 strains of Enterobacteriaceae classified by phenotypes. The comparison of MICs of Timentin and ticarcillin for these strains shows that for penicillinase-producing strains, the Timentin MIC is lower than for ticarcillin whereas cephalosporinase-producing strains have equal MICs for the two. Finally strains that produce many different beta-lactamases are not affected by the presence of clavulanic acid. These results should make it possible to propose provisional zone diameters for determining sensitivity and resistance to Timentin.
Agar↗
Resistance to beta-lactams in Enterobacteriaceae: distribution of phenotypes related to beta-lactamase production.
Phenotypes of susceptibility to amoxycillin (Amo), ticarcillin (Tic), cephalothin (Ctn) were determined in 1366 isolates of Enterobacteriaceae by disk method and beta-lactamases were identified in 243 strains belonging to different phenotypes of amoxycillin-resistant strains. AmoR TicR CtnS strains (25%) were penicillinase producers and all of them were susceptible to the combination amoxycillin/clavulanic acid (Amo/CA) and ticarcillin/clavulanic acid (Tic/CA). Amo1/R TicS CtnR strains (12%) were cephalosporinase producers and resistance to Amo/CA was observed, except for Proteus vulgaris. AmoR TicR CtnR strains (18%) often produced two beta-lactamases (penicillinase and cephalosporinase) and they were resistant to Amo/CA; in this group, susceptibility to Tic/CA depends on the nature and the amount of the beta-lactamase produced, except for Serratia marcescens for which antibiotic resistance is probably due to other mechanisms. Tic/CA resistance was mainly found in Serratia marcescens (41%) and Enterobacter cloacae (36%).
Amoxicillin↗
[In-vitro activity of cefonicid on hospital bacteria. Regression line and proposal for critical values].
Antimicrobial activity of cefonicid, a new second generation cephalosporin, against 315 hospital isolates (4th trimester 1984) was investigated. E. coli and Proteus mirabilis were the most susceptible species. All E. coli strains except one were inhibited at 8 mg/l (modal MIC: 0.5); MICs of all indole + Proteus were 8 mg/l (modal MIC: 0.06). Another group was moderately susceptible: MICs of Klebsiella and Citrobacter ranged from 0.12 to 128 mg/l, but MICs of 50% of these strains were less than or equal to 4 mg/l; MIC was less than or equal to 8 mg/l for 75% of indole + Proteus and Providencia strains; tested Proteus vulgaris were especially resistant (MICs greater than 128 mg/l). Most Enterobacter and Serratia strains showed little susceptibility (modal MIC for both species greater than or equal to 128 mg/l). MICs of all tested Pseudomonas aeruginosa strains were greater than 128 mg/l. 20 of the 24 tested Acinetobacter strains had a MIC of greater than or equal to 128 mg/l. For Staphylococcus aureus, 88% of methicillin-sensitive strains were inhibited by concentrations of 2 to 4 mg/l whereas methicillin-resistant strains were resistant to cefonicid (75%: MIC greater than 64 mg/l). Enterococci were resistant to cefonicid. A correlation curve was established (Enterobacteria and Staphylococci). On the basis of cefonicid's pharmacokinetic characteristics, critical concentrations are proposed.
Bacteria↗
[In vitro activity of a new 3d-generation cephalosporin, cefodizime, on hospital bacteria].
Minimal inhibitory concentrations (MICs) of cefodizime were evaluated by agar dilution for 746 bacterial strains isolated in two hospitals. For enterobacteriaceae MICs ranged from 0.008 micrograms/ml to more than 128 micrograms/ml (mode MIC: 0.25); mode MICs varied across species, ranging from 0.016 micrograms/ml for Proteus mirabilis to 1 microgram/ml for Citrobacter; MICs ranged from 0.12 to 8 for most Enterobacter and from 1 to 64 for Serratia. The rare cefotaxime-resistant strains, most of which were Citrobacter or Enterobacter, also showed resistance to cefodizime. Cefodizime was noticeably less active against Pseudomonas aeruginosa and Acinetobacter, with MICs ranging from 32 to more than 128. Haemophilus sp. and Gonococci, regardless of beta-lactamase-production status, as well as Neisseria meningitidis, were highly susceptible (MIC less than or equal to 0.008-0.016). Cefodizime was moderately active against methicillin-susceptible Staphylococci (MIC: 2 to 16 micrograms/ml) and failed to inhibit methicillin-resistant strains. Enterococci were slightly susceptible or resistant. Whereas the other Streptococci and Pneumococci had low MICs (0.03-0.12). A fairly wide range of MICs was found for anaerobes, with lower values for Clostridium (0.008 to 1) than for Bacteroids (8 to 128 mu g/ml). Our results show that cefodizime has the same properties as other third-generation cephalosporins: cefotaxime-resistant Enterobacteriaceae strains also exhibit resistance to cefodizime.
Bacteria↗
[In vitro activity of ceftriaxone on hospital bacteria. Results of a multicenter study].
Minimal inhibitory concentrations (MICs) of ceftriaxone were determined by agar dilution for 2 099 strains isolated in six teaching hospitals. MICs were less than 1 microgram/ml for the great majority of Enterobacteriaceae, with mode MICs varying across groups from less than 0.008 micrograms/ml for Proteus (mirabilis and indole-positive) to 0.25 for Enterobacter. Only a few resistant strains were found, mainly among Enterobacter and Citrobacter. Ceftriaxone proved noticeably less active against P. aeruginosa and Acinetobacter (mode MICs: 16 micrograms/ml). Haemophilus sp. and Gonococci, regardless of beta-lactamase production status, as well as Neisseria meningitidis, were highly susceptible (MIC less than 0.008-0.032). Ceftriaxone was moderately active against methicillin-susceptible staphylococci (MIC: 2 to 8 micrograms/ml) and failed to inhibit methicillin resistant strains. Enterococci were slightly susceptible or resistant, whereas the other Streptococci and Pneumococci had low MICs (0.03-0.25). A fairly wide range of MICs was found for anaerobes (Clostridium: 0.06-2, Bacteroides: 0.5-32). Our data show that its particularly strong activity against Proteus, Haemophilus and Neisseria sets ceftriaxone apart from the other third-generation cephalosporins.
Acinetobacter↗
[Carbenicillin resistance of gram-negative bacteria: incidence, biochemical and genetic determinism].
Of nine hundred ampicillin resistant (Amp-R) enterobacteria strains, isolated in hospital between July and December 1981, 73,7% are also carbenicillin-resistant (Carb-R). This particular double resistance varies depending upon the species considered: indole positive Proteus (23%), Enterobacter cloacae (64%), Citrobacter freundii (67%), Acinetobacter calcoaceticus (73%), Proteus mirabilis (75%), Serratia marcescens (90%), Escherichia coli (91%), Providencia stuartii (96%) and Klebsiella pneumoniae (100%). The biochemical and genetic basis of resistance to beta-lactamines was studied in 27 strains belonging to these 9 species. A constitutive beta-lactamase was found in all the strains. These enzymes were identified by determination of the isoelectric point on crude sonic extracts, the enzymic activity profile, the inhibition by clavulanic acid and cloxacillin of enzyme activity. Two types of enzymes were predominant: TEM-1 (20 strains) and TEM-2 (7 strains); two strains of Klebsiella pneumoniae produced both SHV-1 and TEM-1. The transfer by conjugation to E. coli K12 of ampicillin and carbenicillin resistance was obtained with 14 strains: (E. coli: 9, C. freundii: 1, K. pneumoniae: 1, E. cloacae: 2, P. stuartii: 1). In all strains but one E. coli we noted the co-transfer of other antibiotic resistance markers.
Ampicillin↗
[Protected distal aspiration in the identification of pathogenic microorganisms in pneumologic intensive care].
To identify the micro-organisms responsible for bronchopulmonary infections in intensive care patients is an absolute prerequisite to successful treatment. Numerous techniques of specimen collection have been used to facilitate this bacteriological diagnosis. In this study, which involved 27 intensive care patients selected according to various criteria of infection, endotracheal aspiration (a commonly used but not very specific technique) was compared with protected distal brushing under fibroscopy and with protected distal aspiration. The latter method, still seldom used, proved as specific as protected distal brushing (hitherto regarded as the reference method), but it also presents the enormous advantages of being rapid, non-traumatic, devoid of side-effects and easily performed in hospital routine by paramedical staff.
Adult↗
[In vitro effect of ceftriaxone on hospital bacteria. Line of regression and critical values].
Antimicrobial activity of ceftriaxone, a new third generation cephalosporin, against hospital isolates was investigated. 312 strains belonging to the most commonly recovered species were studied using the following methods: agar diffusion (disk antibiotic testing), agar dilution (determination of MIC) and dilution in a liquid medium with subculture to agar plates (determination of MBC). Except for a few Citrobacter strains and rare Serratia strains, all Enterobacteriaceae tested proved highly susceptible, with MICs less than or equal to 1 mg/l and mode MICs ranging from 0.003 mg/l (Proteus) to 0.25 mg/l (Enterobacter). MICs ranged from 16 to 32 mg/l for Acinetobacter (mode MICs: 16 mg/l) and 16 to greater than or equal to 128 for Pseudomonas (mode MIC greater than or equal to 128 mg/l). Methicillin-susceptible staphylococci were moderately susceptible to ceftriaxone (MIC: 2 to 8 mg/l) whereas methicillin-resistant staphylococci and enterococci were resistant (MIC greater than or equal to 64 mg/l). Bactericidal activity was excellent: MBC/MIC less than or equal to 2 (except for a few Serratia strains). A correlation curve was established. Given the high serum concentrations of ceftriaxone (achieved with the usual maximal dosage) and its unusually extended half-life (7 to 8 h), the following cutoff concentrations can be proposed: C less than or equal to 4 mg/l, corresponding to greater than or equal to 20 mm: susceptible bacteria C greater than 32 mg/l, corresponding to less than 15 mm: resistant bacteria.
Acinetobacter↗
[Comparative multicenter study of 2 methods of determining sensitivity to antibiotics. Gel diffusion method and semiautomatic method in fluid ABAC medium].
Susceptibility of 60 bacterial isolates to 15 antibiotics was determined by two methods in three laboratories: 48 Gram negative bacilli and 12 Staphylococci were selected because of "intermediate" susceptibility to at least one antibiotic. Results show a good correlation between the two methods: more than 90% for carbenicillin, cefazolin, cefoxitin, cefamandole, kanamycin, tobramycin, amikacin, erythromycin, pristinamycin and fusidic acid, between 80 and 90% for penicillin G, ampicillin, oxacillin, gentamicin, doxycycline, chloramphenicol, spiramycin and clindamycin, less than 80% for neomycin, tetracycline, minocycline and oleandomycin. Interpretation criteria are different in the two methods for rifampicin, colistin and cotrimoxazole. Between the three laboratories, correlation was 90,3% and 88,6% for disc diffusion method and ABAC system respectively.
Anti-Bacterial Agents↗
[Comparative activity of sulfamethoxazole-trimethoprim (SMZ-TMP) on bacteria responsible for ORL infections].
The bacteriostatic activity in vitro of co-trimoxazole (SMZ-TMP); ampicillin, tetracycline and oleandomycin was evaluated against 225 bacterial strains. All the strains (49 Pneumococci, 49 Haemophilus, 41 Streptococci and 86 Staphylococcus aureus) were isolated from sinusitis (63 strains) and otitis (162 strains) in monomicrobial samples. The minimal inhibitory concentrations (MICs) of the 4 antibiotics were determined by the agar diffusion method on all strains. Moreover MICs of SMZ-TMP were determined by the broth dilution method on Haemophilus strains. Seventy seven p. cent of the strains were found sensitive to SMZ-TMP, 70.7% to ampicillin, 85.4% to tetracycline and 73% to oleandomycin. SMZ-TMP was the most effective on Staphylococcus aureus (80% of the isolates were sensitive), whereas ampicillin was effective on all Streptococcus, and Pneumococcus strains and tetracycline was the most active on Haemophilus strains (88% of the isolates were sensitive).
Ampicillin↗
[In vitro activity of combinations of cefotaxime and moxalactam with aminoglycosides on beta-lactamase-producing Enterobacteriaceae].
The in vitro synergistic activities of cefotaxime (Ctx) or moxalactam (Mox) in combination with gentamicin, amikacin, dibekacin or netilmicin were compared against 15 beta-lactamases non-producing or producing isolates of Enterobacteriaceae. The strains were classified according to their resistance to ampicillin (Am), carbenicillin (Cb) and cephalotin (Ce), but all were sensitive to the antibiotics tested in combination. In vitro checkerboard studies were performed using a microtiter technique for the selected strains. The FIC index was less than or equal to 0.62 for AmR CbR CeR strains (E. coli, E. cloacae, Serratia), for AmR CbS CeR strains (E. cloacae, Serratia, P. vulgaris) and for AmS CbS CeR strains (Serratia, P. morganii). These combinations were frequently additive (FIC = 0.75 - 1.0) against the AmS CbS CeS or AmR CbR CeS strains. Thus, the synergistic activities of Ctx and Mox in combination with an aminoglycoside seem to be correlated with beta-lactamase type produced by the Enterobacteriaceae.
Aminoglycosides↗