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Biomedical subjects

A Philippon

Publications and source records attributed to A Philippon.

At least 145 records · Page 8Linked to original sources

Epidemiology of extended spectrum beta-lactamases.

Beta-lactamases play a major part in resistance, as recently redemonstrated by the emergence of extended spectrum beta-lactamases. Since its discovery in FR Germany, SHV-2 has been reported from four continents and CTX-1 (TEM-3) was established in at least 26 French hospitals. More than 12 other enzymes have been individualized. The newest aspect of resistance was probably underestimated because most strains of enterobacteria (mainly Klebsiella pneumoniae) appeared susceptible to oxyimino-beta-lactams as suggested by MICs or diameters of inhibition zone sizes. The double-disk synergy test between amoxicillin/clavulanic acid and oxyimino-beta-lactams was useful to easily detect two susceptibility patterns (CTX, CAZ). Extended spectrum beta-lactamases isolated among nosocomial isolates of enterobacteria (urines, blood, wound, sputum cultures) mostly from intensive care units have spread through hospitals. If outbreaks were described, numerous serotypes were identified in Klebsiella pneumoniae. In France the distribution of extended spectrum beta-lactamases showed that CTX-1 (TEM-3) was well distributed among ten species unlike SHV-type enzymes (SHV-2, SHV-3, SHV-4) preferentially detected in Klebsiella pneumoniae. A majority of strains produced CAZ-type enzymes in Escherichia coli. Some isolates produced two extended spectrum beta-lactamases. In Tunisia extended spectrum beta-lactamase producing strains were mainly identified among pediatric isolates of Klebsiella pneumoniae, Salmonella and Escherichia coli; SHV-2 was predominant but recently CTX-1 and two other types with an isoelectric point of 6.35 and 5.4 (phenotype CTX) were individualized. Because plasmid-encoded, this mechanism was spreading in France among enterobacteria with other resistance markers (e.g. netilmicin, amikacin) for CTX-1 unlike SHV-2.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Infections↗

Characterization of a beta-lactamase from Pasteurella multocida.

A bovine strain of Pasteurella multocida was found to produce a beta-lactamase. The minimal inhibitory concentrations of amoxicillin (128 mg/l) and ticarcillin (512 mg/l) were high for this strain. The enzyme was periplasmic and produced constitutively, and there was no obvious permeability barrier. This enzyme had a TEM-substrate profile, and no inhibition was detected with antisera (anti-TEM-1, anti-TEM-2). The apparent isoelectric point was estimated at 8.8.

Amoxicillin↗

Extended broad-spectrum beta-lactamases conferring transferable resistance to newer beta-lactam agents in Enterobacteriaceae: hospital prevalence and susceptibility patterns.

Before 1985 at the Pitié-Salpêtrière Hospital in Paris (2,400 beds), resistance to cefotaxime in clinical isolates of Enterobacteriaceae involved only species producing inducible class 1 beta-lactamase. Between November 1985 and April 1987, however, 62 isolates (57 of Klebsiella pneumoniae and five of Escherichia coli) showed decreased susceptibility to cefotaxime (mean MIC, 8-16 micrograms/mL). The transferability of cefotaxime resistance in E. coli K12 was demonstrated for 15 of 16 selected isolates. By isoelectric focusing using iodometric detection with 20 mg of ceftriaxone/100 mL and determination of substrate and inhibition profiles, three beta-lactamases mediating cefotaxime resistance were identified as SHV-2 (isoelectric point [pI] 7.6), CTX-1 (pI 6.3), and "SHV-2-type" or SHV-3 (pI 6.98). The three beta-lactamases hydrolyzed penicillins and cephalosporins (including cefotaxime and ceftriaxone) and were therefore designated "extended broad-spectrum beta-lactamases" (EBS-Bla). The enzymes conferred to derivatives a high level of resistance to amoxicillin, ticarcillin, piperacillin, and cephalothin and a decreased degree of susceptibility (i.e., MICs increased by 10- to 800-fold) to cefotaxime, ceftriaxone, ceftazidime, and aztreonam. These beta-lactamases did not affect the activity of cephamycins (cefoxitin, cefotetan, moxalactam) or imipenem. Synergy between clavulanate or sulbactam (2 micrograms/mL) and amoxicillin was greater against derivatives producing EBS-Bla than against those producing TEM-1, TEM-2, or SHV-1; this synergy was greater with clavulanate than with sulbactam against derivatives producing SHV-2 and the SHV-2-type enzyme but was similar with clavulanate and sulbactam against those producing CTX-1. A double-disk synergy test performed with cefotaxime and Augmentin disks (placed 30 mm apart, center to center) seemed a useful and specific test for the detection of strains producing EBS-Bla.

Anti-Bacterial Agents↗

[Beta-lactamases of Gram negative bacteria: never-ending clockwork!].

The acquired resistance against the wide-spectrum and highly stable beta-lactams including third-generation cephalosporins (3GC) and carbapenems is constinuously increasing and widespead with the discovery of various plasmid-encoded, or genes cassette or integrons coding for a novel beta-lactamase, always a major mechanism of resistance. To explain resistance against 3GC, with the continuing story with TEM and SHV mutated enzymes, several types of ESBL (class A) emerge the CTX-M type, at least CTX-M-40, but also other non predominant types intitled BES, GES, PLA, PER, VEB. The wider resistance including 3GC, cephamycins and beta-lactamase inhibitor is correlated to synthesis of transferable cephalosporinases (class C) usually located in the chromosome but mobilized from Enterobacter spp., Citrobacter freundii, Hafnia alvei, Morganella morganii, Aeromonas caviae. Such genes encoded the following types: ACC-1, ACT-1, CFE-1, CMY group, DHA-1, FOX group, MIR-1, MOX-1. Finally the resistance against carbapemens e.g. imipenem originally restricted to Pseudomonas aeruginosa, then to Acinetobacter baumannii and finally to enterobacteria is related to production of novel enzymes (classes B, D and A) denominated IMP, VIM SME, GIM, OXA, KPC. A striking exemple of evolution towards more and more resistance is given by Salmonella, even from animal origins, a great threat fo public health. So far it appears necessary to perform molecular approaches to identify such enzymatic production. Finally because the absence of real new drugs, the discovery of some progenitors of the gene beta-lactamase, a strict control of beta-lactam antibiotics must be provide not only in medecine or veterinary field but also in agriculture, including aquaculture for example.

Animals↗

Immunological comparison of constitutive beta-lactamases of gram-negative bacteria by neutralization in zymogram gels: properties of anti-TEM-1 and anti-TEM-2 sera.

The zymogram technique was applied to a beta-lactamase neutralization assay with anti-TEM-1 and anti-TEM-2 sera. Both were shown to contain neutralizing antibodies directed towards various beta-lactamases of Gram-negative bacteria. The quantitative neutralization allowed classification into five groups of the 28 beta-lactamases used as standards and 61 from clinical isolates. In the first were enzymes such as TEM-1 and TEM-2 including TLE-1, SHV-1, SHV-2, penicillinases of Klebsiella pneumoniae and CTX-1. Partial neutralization distinguished two groups containing the CARB group of enzymes, which are different from PSE-2 and PSE-3, and the MAL penicillinases of Levinea malonatica, which are different from L. amalonatica enzymes. Broad spectrum beta-lactamases of K. oxytoca constituted a unique group of partially neutralized enzymes. Among the beta-lactamases not neutralized by either serum were the plasmid-mediated OXA-enzymes, various species-specific beta-lactamases and cephalosporinases. The antigenic similarities of the enzymes appeared to correlate with the extent of similarities of their catalytic properties, namely those of penicillinases. Such comparisons between the beta-lactamase groups provide an indirect approach to the physiological and structural analysis of established and recently evolved beta-lactamases.

Epitopes↗

[Beta-lactamases of ampicillin-resistant Salmonella].

One hundred and five strains of Salmonella, including 103 clinical isolates, were examined for resistance to beta-lactams (ampicillin, carbenicillin). The resistance frequency was 5.9 and 40.6%, respectively, according to the geographical source: France or Senegal. The mechanism of resistance to beta-lactam antibiotics was always related to the biosynthesis of one constitutive beta-lactamase (beta la+). By analytical isoelectric focusing on gel of all crude sonic extracts, four types of enzymes were identified: TEM-1, TEM-2, OXA-1 and SHV -1. TEM-1, the most prevalent, was observed among 17 serotypes, TEM-2 among 3 including S. poona , and OXA-1 among 2 serotypes. SHV -1 was detected in all isolates of S. ordonez (38) but only among strains of this serotype. Among others factors involved in their distribution, differences were reported according to the geographical origin of the studied strains. In France, the three types, TEM-1, TEM-2 and OXA-1, were isolated only in the north. Moreover, the resistance frequency was 4-fold higher (7.3%) than in the south (1.8%). In Africa (Senegal), three types were individualized: TEM-1, TEM-2 and SHV -1. The SHV -1 type was only detected in clinical isolates of S. ordonez from Senegal, all of which were multi-resistant to other antibiotics (chloramphenicol, sulfonamides and tetracyclines).

Ampicillin↗