Biomedical subjects

Jan Walther-Rasmussen

Publications and source records attributed to Jan Walther-Rasmussen.

4 recordsLinked to original sources

PubMed2006

OXA-type carbapenemases.

In recent years, the number of class D beta-lactamases with carbapenem-hydrolysing properties has increased substantially. Based on amino acid sequence identities, these class D or OXA-type carbapenemases are divided into eight distantly related groups, and they are only remotely related to other class D beta-lactamases. A putative ancestor to one of the plasmid-encoded OXA-type carbapenemases has been found. OXA-type carbapenemases are not integrated into integrons as gene cassettes like many class D oxacillinases, but most of the OXA-type carbapenemases are instead encoded by chromosomal genes. Some of these OXA-type carbapenemases are widely dispersed in Pseudomonas aeruginosa and especially in Acinetobacter baumannii. Although most of the OXA-type carbapenemases show only weak carbapenemase activity, carbapenem resistance may result from a combined action an OXA-type carbapenemase and a secondary resistance mechanism such as porin deficiencies or overexpressed efflux pumps. This article reviews the phylogeny and the genetic environments of the encoding genes and kinetic properties of the OXA-type carbapenemases.

Acinetobacter baumannii↗

PubMed2006

Extended-spectrum beta-lactamases in Taiwan: epidemiology, detection, treatment and infection control.

Extended-spectrum beta-lactamases (ESBLs) efficiently hydrolyze extended-spectrum beta-lactams such as cefotaxime, ceftriaxone, ceftazidime, and aztreonam. ESBLs are most often plasmid-mediated. In Taiwan, the prevalence of ESBLs in bacteria has risen, ranging from 8.5 to 29.8% in Klebsiella pneumoniae and 1.5 to 16.7% in Escherichia coli isolates. The most prevalent types of ESBLs are SHV-5, SHV-12, CTX-M-3, and CTX-M-14 in isolates of K. pneumoniae and E. coli, with differences between institutions. SHV-12 and CTX-M-3 have been reported as the most common ESBLs in isolates of Enterobacter cloacae and Serratia marcescens, respectively. Molecular epidemiology studies suggest that the ESBL-encoding genes have been disseminated either by proliferation of epidemic strains or by transfer of plasmids carrying the resistance traits. The current ESBL screen guidelines of the Clinical and Laboratory Standards Institute (formerly National Committee for Clinical Laboratory Standards) are issued for E. coli, Klebsiella spp., and Proteus mirabilis. Owing to the lack of standard methods, it remains difficult to assure the presence of ESBL in an isolate co-harboring an AmpC beta-lactamase, particularly in cases where the latter is produced in larger amounts than the former. Empirical therapy with piperacillin-tazobactam to replace third-generation cephalosporins may help to reduce the occurrence of ESBLs in an institution with a high prevalence of ESBL producers. Carbapenems remain the drugs of choice for serious infections caused by ESBL-producing organisms. To retard the selection for carbapenem-resistant bacteria, 7-alpha-methoxy beta-lactams or fourth-generation cephalosporins can be therapeutic alternatives for mild-to-moderate infections provided that the pharmacokinetic and pharmacodynamic target can be easily achieved.

Carbapenems↗

PubMed2004

Cefotaximases (CTX-M-ases), an expanding family of extended-spectrum beta-lactamases.

Among the extended-spectrum beta-lactamases, the cefotaximases (CTX-M-ases) constitute a rapidly growing cluster of enzymes that have disseminated geographically. The CTX-M-ases, which hydrolyze cefotaxime efficiently, are mostly encoded by transferable plasmids, and the enzymes have been found predominantly in Enterobacteriaceae, most prevalently in Escherichia coli, Salmonella typhimurium, Klebsiella pneumoniae, and Proteus mirabilis. Isolates of Vibrio cholerae, Acinetobacter baumannii, and Aeromonas hydrophila encoding CTX-M-ases have also been reported. The CTX-M-ases belong to the molecular class A beta-lactamases, and the enzymes are functionally characterized as extended-spectrum beta-lactamases. This group of beta-lactamases confers resistance to penicillins, extended-spectrum cephalosporins, and monobactams, and the enzymes are inhibited by clavulanate, sulbactam, and tazobactam. Typically, the CTX-M-ases hydrolyze cefotaxime more efficiently than ceftazidime, which is reflected in substantially higher MICs to cefotaxime than to ceftazidime. Phylogenetically, the CTX-M-ases are divided into four subfamilies that seem to have descended from chromosomal beta-lactamases of Kluyvera spp. Insertion sequences, especially ISEcp1, have been found adjacent to genes encoding enzymes of all four subfamilies. The class I integron-associated orf513 also seems to be involved in the mobilization of blaCTX-M genes. This review discusses the phylogeny and the hydrolytic properties of the CTX-M-ases, as well as their geographic occurrence and mode of spread.

Cefotaxime↗

PubMed2002

Plasmid-borne AmpC beta-lactamases.

Historically, it was thought that ampC genes encoding class C beta-lactamases were located solely on the chromosome but, within the last 12 years, an increasing number of ampC genes have been found on plasmids. These have mostly been acquired by ampC-deficient pathogenic bacteria, which consequently are supplied with new and additional resistance phenotypes. This review discusses the phylogenetic origin of the plasmid-encoded AmpC beta-lactamases, their occurrence, and mode of spread, as well as their hydrolytic properties.

Bacterial Proteins↗