Carbapenem-hydrolysing metallo-beta-lactamases from Klebsiella pneumoniae and Escherichia coli isolated in Australia.
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Animals↗
Biomedical subjects
P Nordmann
Publications and source records attributed to P Nordmann.
First description of CTX-M-15-producing Klebsiella pneumoniae in Turkey.
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Humans↗
[Mechanisms of resistance to betalactam antibiotics in Pseudomonas aeruginosa].
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Bacterial Proteins↗
Emerging carbapenemases in Gram-negative aerobes.
Carbapenemases may be defined as beta-lactamases that significantly hydrolyze at least imipenem or/and meropenem. Carbapenemases involved in acquired resistance are of Ambler molecular classes A, B, and D. Class A, clavulanic acid-inhibited carbapenemases are rare. They are either chromosomally encoded (NMC-A, Sme-1 to Sme-3, IMI-1) in Enterobacter cloacae and Serratia marcescens, or plasmid encoded, such as KPC-1 in Klebsiella pneumoniae and GES-2 in Pseudomonas aeruginosa, the latter being a point-mutant of the clavulanic acid-inhibited extended-spectrum beta-lactamase GES-1. The class B enzymes are the most clinically significant carbapenemases. They are metalloenzymes of the IMP or VIM series. They have been reported worldwide but mostly from South East Asia and Europe. Metalloenzymes, whose genes are plasmid and integron located, hydrolyze virtually all beta-lactams except aztreonam. Finally, the class D carbapenemases are increasingly reported in Acinetobacter baumannii but compromise imipenem and meropenem susceptibility only marginally. The sources of the acquired carbapenemase genes remain unknown, as does the relative importance of the spread of epidemic strains as opposed to the spread of plasmid- or integron-borne genes. Because most of these carbapenemases confer only reduced susceptibility to carbapenems in Enterobacteriaceae, they may remain underestimated as a consequence of the lack of their detection.
Amino Acid Sequence↗
Acquired carbapenem-hydrolyzing beta-lactamases and their genetic support.
Carbapenem-hydrolyzing beta-lactamases of several Ambler molecular classes have been reported as the source of acquired beta-lactam antibiotic resistance in Gram negative bacteria. The metallo-enzymes of Ambler class B are the most prevalent enzymes in this case. These clavulanic-acid resistant enzymes have a large spectrum of hydrolysis including penicillins, cephalosporins (third and fourth generations), carbapenems but not monobactams. They are responsible for acquired resistance in several Gram negative species of clinical relevance in human medicine. IMP-1 was the first reported as acquired in Japan, mostly from Serratia marcescens and Pseudomonas aeruginosa isolates, and has been detected in Europe recently. Several variants of IMP-1 (IMP-2 to -9) have been characterized, possessing 85 to 99% amino acid identity, mostly from P. aeruginosa isolates. In addition, VIM-1 to -3 beta-lactamases have also been described, first in Europe (Italy, France, and Greece) and now in Korea. The VIM series shares 30% amino acid identity with the IMP-series. Most of these class B enzymes have genes that are integron- and plasmid-located. Finally, a few Ambler class A (SME-1, NMC-A, IMI-1, KPC-1) and class D (OXA-23 to -27) beta-lactamases involved in carbapenem hydrolysis have been reported also from rare isolates of Gram-negative rods. This review underlines the worldwide spread of carbapenem-hydrolyzing beta-lactamases as representing an important threat for efficacy of antibiotics in the near future.
Amino Acid Sequence↗
[Contribution of systematic culture of drainage fluids in Altemeier class 1 and 2 procedures].
PURPOSE OF THE STUDY: We conducted a prospective study to determine the therapeutic impact of systematic culture of suction drainage collections in Altemeier class I and II procedures. MATERIALS AND METHODS: We examined the following questions: how many microbiologically positive samples and infections of the operative site were present in the included patients? for positive cases, what was the antibiotic prescription (excluding antibiotic prophylaxy protocols planned before surgery for cleaning)? if the sample was positive in a patient with no clinical infection, what antibiotics were prescribed? RESULTS: A total of 1039 samples were collected in 470 patients undergoing Altemeier class I and II procedures. One hundred five cultures were positive in 34 patients who had undergone major surgery. There were 11 postoperative infections during the study period. Mean delay to diagnosis of infection was 19.5 days. Only one infected patient with positive drainage samples developed an infection on the 7(th) day; the causal germ was different from that identified in the drainage collection. Only one of the patients with a positive drainage sample was given antibiotics, but this treatment was initiated at peroperative reception of the laboratory results. DISCUSSION: Our findings demonstrate that systematic samples of drainage collections make no contribution to therapeutic decision making in patients undergoing class I and II surgery.
Bacteria↗
[Encephalopathy associated with severe bacterial infections: "presuppurative encephalitis" or "toxi-infectious disorder"?].
Three children are reported, exhibiting encephalopathic symptoms in the course of a severe bacterial infection, though they had no sign of intracranial purulent collection nor metabolic disturbances: the first was associated with a appendicular peritonitis, the second with a purulent knee arthritis, the third with a pneumoccus septicemia. The elements are reviewed that favor either a true septic encephalitis, i.e. microscopic presuppurative foci, versus a toxiinfectious process, either by direct action of toxins or through intracerebral activation of pre-inflammatory cytokines. Whatever the mechanism involved in individual cases, the treatment is mainly based on prompt administration of the convenient antibiotics.
Adolescent↗
Plasmid-mediated extended-spectrum beta-lactamase (CTX-M-3 like) from India and gene association with insertion sequence ISEcp1.
Six non-clonally related enterobacterial isolates producing a same extended-spectrum beta-lactamase CTX-M-15 were isolated in 1999 from patients hospitalized in a New Delhi hospital. CTX-M-15 differed from CTX-M-3 by an asparagine to glycine substitution in position ABL238. Its gene was located on large plasmids varying in size. In each case, a same insertion sequence ISEcp1 was identified upstream of the 5' end of bla(CTX-M-15). Typical -35 and -10 promoter sequences of Enterobacteriaceae were identified in the 3' end of ISEcp1. The location of ISEcp1 upstream of plasmid-mediated CTX-M-type beta-lactamase genes may contribute to their spread or/and their expression.
Amino Acid Sequence↗
Molecular identification of TEM-1 beta-lactamase in a Pasteurella multocida isolate of human origin.
Two clinical strains of Pasteurella multocida were isolated from an HIV-infected patient who developed arthritis. Strain FB-1, which was isolated from a dog-bite wound, was resistant to narrow-spectrum penicillins. The second strain, FB-2, which was present in blood cultures as well as the dog-bite wound, was susceptible to all beta-lactam agents. Arbitrarily primedpolymerase chain reaction and pulsed-field gel electrophoresis revealed that these two isolates were genetically indistinguishable. 16S rDNA gene sequencing facilitated identification at the subspecies level. Amoxicillin resistance determinant was located on a highly unstable 4.3-kb plasmid, pFAB-1. Isoelectrofocusing and polymerase chain reaction amplification followed by sequencing revealed the presence of a pI 5.4 TEM-1 beta-lactamase. This description is the first of a TEM-1 Beta-lactamase' in a Pasteurella multocida strain of human origin.
Acquired Immunodeficiency Syndrome↗
Multicenter evaluation of an automated system using selected bacteria that harbor challenging and clinically relevant mechanisms of resistance to antibiotics.
A multicenter study was carried out to evaluate the performance of a new commercial automated system in comparison with that of the reference agar dilution method. Ten clinical microbiology laboratories tested a collection of 61 strains of gram-negative bacilli (49 Enterobacteriaceae and 12 Pseudomonas aeruginosa), and 6 other laboratories tested a collection of 55 strains of gram-positive cocci (10 enterococci and 45 staphylococci) against 10-20 antimicrobial agents. The strains were selected on the basis that they harbored challenging and characterized mechanisms of resistance. In comparison with the agar reference method, the automated system gave an overall essential agreement (+/-1 dilution) of 94.5%, 93.5%, and 97% for the gram-negative bacilli, enterococci, and staphylococci, respectively. According to the interpretive standards of the National Committee for Clinical Laboratory Standards, the category agreement ranged from 96 to 96.4% for the three sets of organisms. The accuracy of the automated system, as determined by the kappa test, ranged from 0.80 to 0.88, reflecting an almost perfect agreement with the reference technique. Very major, major, and minor errors obtained with the automated system were 0.3%, 2.9%, and 6.6% for gram-negative bacilli, 3.4%, 0%, and 5% for enterococci, and 1%, 1.6%, and 2.7% for staphylococci, respectively. The high rate of very major errors in enterococci was mostly due to a single strain of multidrug-resistant Enterococcus faecium, which was found susceptible to several antibiotics in a majority of participant laboratories. The use of a heavy inoculum and of a broth test medium by the automated system might account for a better expression of certain resistance mechanisms, including beta-lactamases, as compared to the agar dilution reference method. The interlaboratory reproducibility was acceptable, as shown by the narrow dispersion of MICs and by the results of quality control.
Anti-Bacterial Agents↗
Unusual etiology of visual loss in an HIV-infected patient due to endogenous endophthalmitis.
Disseminated candidiasis, especially ocular infections such as endophthalmitis, is uncommon in HIV-infected patients. We report a case of candidal endophthalmitis in an HIV-positive non-drug-user patient, following candidemia from a cutaneous abscess at the site of a peripheral catheter. Ocular disease was revealed by a visual decrease in the left eye. DNA analysis using RAPD showed identical patterns of Candida albicans isolated from the skin and eye. Combination therapy with high-dose fluconazole and intravenous amphotericin B was performed. Two intravitreal amphotericin B injections and a vitrectomy were administered because of an amblyopic right eye and severe vitritis. The outcome was favorable without relapse at 18 months.
AIDS-Related Opportunistic Infections↗
In vivo selection of oxacillinase-mediated ceftazidime resistance in Pseudomonas aeruginosa.
Ceftazidime-susceptible and -resistant Pseudomonas aeruginosa strains were isolated from pulmonary specimens following a treatment with ceftazidime in a patient who developed a nosocomial pneumonia. The ceftazidime-susceptible and -resistant strains were clonally related and harbored a self-transferable approximately 155-kb plasmid. These isolates expressed two OXA-10-like oxacillinases, the narrow-spectrum OXA-35 and the expanded-spectrum OXA-19, respectively, differing by one amino acid substitution. This is the first example of in vivo selection of an extended-spectrum oxacillinase from a restricted-spectrum oxacillinase.
Amino Acid Sequence↗
Plasmid-mediated and inducible cephalosporinase DHA-2 from Klebsiella pneumoniae.
A Klebsiella pneumoniae strain resistant to cefoxitin and oxyimino-cephalosporins was cultured from a child hospitalized in Paris, France, in 1992. This isolate harboured a beta-lactamase gene located on an approximately 200 kb non-self-transferable plasmid. The beta-lactamase identified, DHA-2, shared 99% amino acid identity with the AmpC enzyme of Morganella morganii. DHA-2 was a point-mutant derivative of DHA-1 identified previously in a Salmonella enteritidis isolate. DHA-2 expression was inducible due to an ampR regulatory gene. This is the first report of an inducible and plasmid-located cephalosporinase from K. pneumoniae.
Amino Acid Sequence↗
SHV-type extended-spectrum beta-lactamase in a Shigella flexneri clinical isolate.
A Shigella flexneri isolate resistant to oxyimino-cephalosporins was recovered from a stool sample of a 16 month-old Algerian child hospitalized in Paris, France. This isolate harboured an SHV-2 beta-lactamase gene located on a c. 80 kb self-transferable plasmid. This is the first report of an Ambler class A extended-spectrum beta-lactamase from Shigella spp.
Anti-Bacterial Agents↗
OXA-35 is an OXA-10-related beta-lactamase from Pseudomonas aeruginosa.
Pseudomonas aeruginosa clinical isolate PA35 is resistant to amino- and ureido-penicillins, has intermediate susceptibility to cefsulodin, cefepime and aztreonam, and is susceptible to imipenem and ceftazidime. Cloning and sequencing revealed a new beta-lactamase variant, OXA-35, sharing 96% amino acid identity with OXA-10. OXA-35 displays a restricted-substrate hydrolysis profile with improved hydrolysis of amoxicillin and cloxacillin compared with OXA-10. OXA-35 differs from derivatives OXA-19 and OXA-28 by one amino acid substitution and may be a progenitor of these OXA-13-like extended-spectrum beta-lactamases.
Aged↗
Chlorhexidine versus povidone iodine in preventing colonization of continuous epidural catheters in children: a randomized, controlled trial.
BACKGROUND: Chlorhexidine is better than povidone iodine for skin preparation before intravascular device insertion or blood culture collection, but it is not known whether chlorhexidine is superior in reducing colonization of continuous epidural catheters. METHODS: Children requiring an epidural catheter for postoperative analgesia longer than 24 h were randomly assigned to receive skin preparation with an alcoholic solution of 0.5% chlorhexidine or an aqueous solution of 10% povidone iodine before catheter insertion. Using surgical aseptic techniques, catheters were inserted into either the lumbar or the thoracic epidural space based on the preferences of the anesthesia team, on clinical indication, or both. Immediately before epidural catheter removal, their insertion site and hub were qualitatively cultures. After their removal, the catheter tips were quantitatively cultured. Catheters were classified as colonized when their tips yielded 1,000 or more colony-forming units/ml in cultures. RESULTS: Of 100 randomly assigned patients, 96 were evaluable. The clinical characteristics of the patients and the risk factors for infection were similar in the two groups. Catheters were kept in place for a median (range) duration of 50 (range, 21-100) h. Catheters inserted after skin preparation with chlorhexidine were one sixth as likely and less quickly to be colonized as catheters inserted after skin preparation with povidone iodine (1 of 52 catheters [0.9 per 100 catheter days] vs. 5 of 44 catheters [5.6 per 100 catheter days]; relative risk, 0.2 [95% confidence interval, 0.1-1.0]; P = 0.02). Coagulase-negative staphylococci were the only colonizing microorganisms recovered, and the skin surrounding the catheter insertion site was the origin of all the colonizing microorganisms. CONCLUSIONS: Compared with aqueous povidone iodine, the use of alcoholic chlorhexidine for cutaneous antisepsis before epidural catheter insertion reduces the risk of catheter colonization in children.
Adolescent↗
AmpD is required for regulation of expression of NmcA, a carbapenem-hydrolyzing beta-lactamase of Enterobacter cloacae.
To further elucidate the induction process of the carbapenem-hydrolyzing beta-lactamase of Ambler class A, NmcA, ampD genes of the wild-type (WT) strain and of ceftazidime-resistant mutants of Enterobacter cloacae NOR-1 were cloned and tested in transcomplementation experiments. Ceftazidime-resistant E. cloacae NOR-1 mutants exhibited derepressed expression of the AmpC-type cephalosporinase and of the carbapenem-hydrolyzing beta-lactamase NmcA. The ampD genes of Escherichia coli and E. cloacae WT NOR-1 transcomplemented the ceftazidime-resistant E. cloacae NOR-1 mutants to the WT level of beta-lactamase expression, while the mutated ampD alleles of E. cloacae NOR-1 failed to do so. The deduced E. cloacae NOR-1 WT AmpD protein exhibited 95 and 91% amino acid identity with the E. cloacae O29 and E. cloacae 14 WT AmpD proteins, respectively. Of the 12 ceftazidime-resistant E. cloacae NOR-1 strains, 3 had AmpD proteins with amino acid changes, while the others had truncated AmpD proteins. Most of these mutations were located outside the conserved regions that link the AmpD proteins to the cell wall hydrolases. AmpD from E. cloacae NOR-1 is involved in the regulation of expression of both beta-lactamases (NmcA and AmpC), suggesting that structurally unrelated genes may be under the control of an identical genetic system.
Alleles↗
Biochemical-genetic characterization of the chromosomally encoded extended-spectrum class A beta-lactamase from Rahnella aquatilis.
From whole-cell DNA of a clinical isolate of the enterobacterial species Rahnella aquatilis, a beta-lactamase gene was cloned that encoded a chromosomally encoded Ambler class A enzyme, RAHN-1. RAHN-1, with a pI of 7.2, shares 76, 73, and 71% amino acid identity with the extended-spectrum beta-lactamase of chromosomal origin from Serratia fonticola and with the plasmid-mediated beta-lactamases CTX-M-2 and CTX-M-1, respectively. The hydrolysis spectrum of the clavulanic acid-inhibited RAHN-1 was expanded to cephalosporins such as cefuroxime, cefotaxime, and ceftriaxone, but not to ceftazidime. Its expression was not inducible.
Amino Acid Sequence↗