Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Trimethoprim Resistance”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1986

Epidemiology of trimethoprim resistance.

Trimethoprim resistance in the Enterobacteriaceae has been dominated by the spread of two genes encoding different dihydrofolate reductases (types IA and II). The original carriage of these genes was by transferable bacterial plasmids. Now, however, one of these genes is often found to be located on the bacterial chromosome. Two new plasmid-mediated dihydrofolate reductases have been identified. One of these enzymes (type IV) confers a low degree of insusceptibility but is inducible, to give levels 600 times higher than the bacterial host enzyme. The technique used to demonstrate the plasmids that carry the gene for this enzyme suggests that they would not be identified by the plasmid transfer methods in current use.

Animals↗
PubMed1994

Trimethoprim resistance in urinary pathogens in northern Scotland: epidemic spread of a resistance plasmid encoding the type Ib trimethoprim-resistant dihydrofolate reductase.

The prevalence of trimethoprim resistance in enterobacterial urinary pathogens from hospitalised patients in the Angus district of northern Scotland (22.8%) was twice that found in similar isolates from patients attending general practitioners (11.2%). Thirty-three of the 143 trimethoprim-resistant strains were shown to harbour transferable plasmids conferring high-level trimethoprim resistance. In total, 17 different plasmid types were distinguished. Two plasmids, pUK1184 and pUK1185, accounted for 36% of the trimethoprim resistance plasmids and were shown by restriction endonuclease digestion fingerprints to be closely related to plasmid pUK28, previously demonstrated to be endemic in urinary pathogens in the Edinburgh area. Only 21% of the plasmids were shown to encode the type Ia trimethoprim-resistant dihydrofolate reductase, whereas 70% of the trimethoprim resistance plasmids were found to encode the type Ib dihydrofolate reductase. Hybridisation of the trimethoprim resistance plasmids identified in this study with gene probes specific for the integrase genes of transposons Tn7 and Tn21 indicates that the dhfrIa is rarely present within Tn7 or related transposons in these plasmids and may be more prevalent within Tn21-like transposons. In contrast, with the exception of the two endemic plasmids that harboured the dhfrIb gene within a Tn7-like transposon, the majority of dhfrIb genes were not found to be associated with either Tn7- or Tn21-like structures.

Bacteriuria↗
PubMed1987

The genetics of bacterial trimethoprim resistance in tropical areas.

Resistance to trimethoprim in Gram-negative bacteria is largely manifested by two trimethoprim resistant dihydrofolate reductases (types I and II) encoded by genes originally located on resistance plasmids. Although trimethoprim resistance increased markedly after the clinical introduction of trimethoprim in the West, its spread has slowed and, in Edinburgh at least, has actually been declining. This reduction has been accompanied by the migration of a transposon, encoding the type I plasmid resistance gene, into the bacterial chromosome. In tropical areas, the incidence of trimethoprim resistance is very much higher. In Tanzania, it has spilled over into other bacteria outside the Enterobacteriaceae, but it was in India where the major problem existed. The majority (64%) of the Indian Enterobacteriaceae studied were resistant to the drug and most of the resistance genes were located on very large plasmids which also conferred resistance to many other antibacterial drugs. Some Indian plasmids carried a new trimethoprim resistance gene which is not detectable by conventional sensitivity tests and may be spreading unnoticed elsewhere. The proportion of trimethoprim resistance has been related to the volume of antibacterial drugs used.

Drug Resistance↗
PubMed1993

Trimethoprim resistance in South African isolates of aerobic gram-negative faecal flora.

Aerobic gram-negative commensal faecal flora from 362 healthy volunteers was examined for resistance to trimethoprim. Three hundred fifty-seven trimethoprim-resistant organisms were isolated from 272 of the volunteers (297 Escherichia coli, 46 Klebsiella spp., 9 Enterobacter spp. and 7 other species). Trimethoprim resistance was associated with resistance to other antibiotics at the following frequencies: ampicillin 71.4%, tetracycline 88%, cephalosporins 14% and aminoglycosides 4%. High-level resistance to trimethoprim (MIC > or = 1024 mg/l) occurred in 98.6% of the isolates. Trimethoprim resistance was transferable in 51.2% of the isolates. An X+ factor was required to mobilize resistance in a further 3.4%. Resistance to other antibiotics cotransferred with trimethoprim at the following frequencies: ampicillin 55.4%, tetracycline 30%, cephalosporins 1.5% and aminoglycosides 2.6%. Restriction enzyme analysis of 148 plasmids revealed 79 different profiles. Two restriction profiles represented 10.1 and 8.8% of these plasmids, respectively. The large number of different antibiograms and restriction profiles indicates that there is a large gene pool of trimethoprim-resistant organisms in the faecal flora.

Bacteria, Aerobic↗
PubMed2001

Multiple mutations modulate the function of dihydrofolate reductase in trimethoprim-resistant Streptococcus pneumoniae.

Trimethoprim resistance in Streptococcus pneumoniae can be conferred by a single amino acid substitution (I100-L) in dihydrofolate reductase (DHFR), but resistant clinical isolates usually carry multiple DHFR mutations. DHFR genes from five trimethoprim-resistant isolates from the United Kingdom were compared to susceptible isolates and used to transform a susceptible control strain (CP1015). All trimethoprim-resistant isolates and transformants contained the I100-L mutation. The properties of DHFRs from transformants with different combinations of mutations were compared. In a transformant with only the I100-L mutation (R12/T2) and a D92-A mutation also found in the DHFRs of susceptible isolates, the enzyme was much more resistant to trimethoprim inhibition (50% inhibitory concentration [IC50], 4.2 microM) than was the DHFR from strain CP1015 (IC50, 0.09 microM). However, Km values indicated a lower affinity for the enzyme's natural substrates (Km for dihydrofolate [DHF], 3.1 microM for CP1015 and 27.5 microM for R12/T2) and a twofold decrease in the specificity constant. In transformants with additional mutations in the C-terminal portion of the enzyme, Km values for DHF were reduced (9.2 to 15.2 microM), indicating compensation for the lower affinity generated by I100-L. Additional mutations in the N-terminal portion of the enzyme were associated with up to threefold-increased resistance to trimethoprim (IC50 of up to 13.7 microM). It is postulated that carriage of the mutation M53-I-which, like I100-L, corresponds to a trimethoprim binding site in the Escherichia coli DHFR-is responsible for this increase. This study demonstrates that although the I100-L mutation alone may give rise to trimethoprim resistance, additional mutations serve to enhance resistance and modulate the effects of existing mutations on the affinity of DHFR for its natural substrates.

Amino Acid Sequence↗
PubMed1989

Trimethoprim resistance in urinary tract pathogens in two Nigerian hospitals.

One hundred and twenty eight (63.3%) of 202 isolates of Gram-negative bacilli from urinary infections in patients in two Nigerian hospitals were found to be resistant to trimethoprim. Of the trimethoprim-resistant organisms, 111 (86.7%) showed MICs of trimethoprim in excess of 1000 mg/l. Trimethoprim resistance was found to be transferable from 65 (50.8%) of these highly resistant organisms into Escherichia coli EC1005. The trimethoprim-resistant strains obtained in the study were also resistant to at least one other antibiotic of the nine tested.

Anti-Bacterial Agents↗
PubMed1985

Trimethoprim resistance in urinary coliforms from patients in the community: plasmids and R-transfer.

A study of urinary coliform isolates, from patients attending their general practitioner, between 1981 and 1983 showed that 10.2% were resistant to trimethoprim. Forty-four trimethoprim-resistant Escherichia coli were collected for further study and the results compared with those obtained from hospital isolates collected during 1979-80 and 1982. Thirty-two (73%) were highly resistant to trimethoprim (MIC greater than 1024 mg/l) a similar proportion to that in the hospital isolates. The highly resistant isolates bore a close resemblance to the hospital isolates in that 66% carried multiple plasmids, 97% were multiply drug-resistant and all were highly resistant to sulphamethoxazole. The frequency of antimicrobial resistance transfer (59%) was similar to that from the hospital isolates. More than half of the trimethoprim resistance plasmids characterized were indistinguishable in terms of mol.wt and resistance pattern from those found in isolates from the hospital collections. Our results suggest that, whereas trimethoprim-resistant E. coli are less commonly isolated from patients in the community than in hospitals, many of the community isolates may have originated from a hospital source.

Conjugation, Genetic↗
PubMed1990

Transmissible trimethoprim resistance in strains of Escherichia coli isolated from cases of infantile diarrhoea.

Of 190 isolates of Escherichia coli from children aged up to 5 years with diarrhoea, 72 (37.9%) were resistant to trimethoprim and of the 70 isolates tested, 38 transferred high level trimethoprim resistance (MIC greater than 1000 mg/L) into E. coli EC 1005. Of the enterotoxigenic isolates from which trimethoprim resistance was transferred, 41.2% also contained transmissible toxigenic characteristics. All the trimethoprim-resistant isolates were resistant to other antibiotics.

Child, Preschool↗
PubMed2004

Presence of bacteriuria caused by trimethoprim resistant bacteria in patients prescribed antibiotics: multilevel model with practice and individual patient data.

OBJECTIVE: To look for evidence of a relation between antibiotic resistance and prescribing by general practitioners by analysis of prescribing at both practice and individual patient level. DESIGN: Repeated cross-sectional study in 1995 and 1996. SETTING: 28 general practices in the Ninewells Hospital laboratory catchment area, Tayside, Scotland. SUBJECTS REVIEWED: 8833 patients registered with the 28 practices who submitted urine samples for analysis. MAIN OUTCOME MEASURES: Resistance to trimethoprim in bacteria isolated from urine samples at practice and individual level simultaneously in a multilevel model. RESULTS: Practices showed considerable variation in both the prevalence of trimethoprim resistance (26-50% of bacteria isolated) and trimethoprim prescribing (67-357 prescriptions per 100 practice patients). Although variation in prescribing showed no association with resistance at the practice level after adjustment for other factors (P = 0.101), in the multilevel model resistance to trimethoprim was significantly associated with age, sex, and individual-level exposure to trimethoprim (P < 0.001) or to other antibiotics (P = 0.002). The association with trimethoprim resistance was strongest for people recently exposed to trimethoprim, and there was no association for people with trimethoprim exposure more than six months before the date of the urine sample. DISCUSSION: Analysis of practice level data obscured important associations between antibiotic prescribing and resistance. The results support efforts to reduce unnecessary prescribing of antibiotics in the community and show the added value of individual patient data for research on the outcomes of prescribing.

Adolescent↗
PubMed1982

Occurrence of transposable trimethoprim resistance in clinical isolates of Escherichia coli devoid of self-transmissible resistance plasmids.

Fifty trimethoprim-resistant clinical isolates of Escherichia coli, devoid of self transmissible trimethoprim resistance plasmids, were examined for the presence of trimethoprim resistance transposons. Trimethoprim resistance was mobilized from 12 strains by transposition onto plasmid RP4. The trimethoprim resistance transposons isolated comprised two groups: those with and without linked streptomycin resistance.

DNA Transposable Elements↗
PubMed1991

Distribution and transferability of plasmids encoding trimethoprim resistance in urinary pathogens from Greece.

Of 505 strains of Enterobacteriaceae responsible for significant bacteriuria and isolated from hospital patients in two Greek cities in 1989, 151 strains (30%) were resistant to trimethoprim (MIC greater than or equal to 4 mg/L) and 220 (44%) were resistant to sulphamethoxazole (MIC greater than or equal to 64 mg/L); 127 (84%) of the trimethoprim-resistant strains exhibited high-level resistance (MIC greater than 1024 mg/L) and 121 (80%) were additionally resistant to four or more other antibiotics. Plasmids were detected in 141 (93%) of the trimethoprim-resistant strains. Trimethoprim resistance was encoded on self-transmissible plasmids in 79 (52%) of the resistant strains, and in a further seven strains (5%), plasmids coding for trimethoprim resistance could be mobilised by X+ factor. Co-transfer of various other antimicrobial resistances with trimethoprim resistance was observed, tetracycline resistance being the most common. The low degree of linkage observed between trimethoprim resistance and resistance to streptomycin and spectinomycin suggests that Tn7 is relatively uncommon in Greece. Classification of trimethoprim-resistance plasmids on the basis of their antimicrobial-resistance patterns and molecular mass revealed 39 different profiles. Overall, these findings differ from those from other European countries where the prevalence of transferable high-level trimethoprim resistance is low and where chromosomal Tn7-encoded trimethoprim resistance is common.

Bacteriuria↗
PubMed1996

Plasmid pDGO100 contains a second integron with the trimethoprim resistance gene dfrA7 as the inserted cassette.

Southern hybridization analysis of the IncC plasmid pDGO100 showed that, in addition to the well-characterized integron In7, there is a second integron which is located on a 3.6-kb BamHI fragment. This integron also possesses the qacE delta l and sulI genes typically found as part of the 3'-conserved segment of integrons. The 3.6-kb BamHI fragment, when cloned into pUC19 to form pDGO301, conferred resistance to trimethoprim as well as sulfamethoxazole. The DNA sequence of the trimethoprim resistance gene in pDGO301 was determined and it was shown that the gene was precisely inserted as a cassette in an integron with 100% identity to the trimethoprim resistance gene dfrA7.

Base Sequence↗
PubMed1989

Isolation and characterization of dihydrofolate reductase from trimethoprim-susceptible and trimethoprim-resistant Pseudomonas cepacia.

Trimethoprim resistance was investigated in cystic fibrosis isolates of Pseudomonas cepacia. Determination of the MIC of trimethoprim for 111 strains revealed at least two populations of resistant organisms, suggesting the presence of more than one mechanism of resistance. Investigation of the antibiotic target, dihydrofolate reductase, was undertaken in both a susceptible strain and a strain with high-level resistance (MIC, greater than 1,000 micrograms/ml). The enzyme was purified by using ammonium sulfate precipitation, gel filtration, and ion-exchange chromatography. Specific activities, molecular weights, isoelectric points, and substrate kinetics were similar for both enzymes. However, the dihydrofolate reductase from the trimethoprim-resistant strain demonstrated decreased susceptibility to inhibition by trimethoprim and increased susceptibility to inhibition by methotrexate, suggesting that these two enzymes are not identical. We conclude that the mechanism of trimethoprim resistance in this strain with high-level resistance is production of a trimethoprim-resistant dihydrofolate reductase.

Culture Media↗
PubMed1990

Increase of trimethoprim resistance among Shigella species, 1975-1988: analysis of resistance mechanisms.

Trimethoprim (TMP) resistance among Shigella species isolated from Finnish travelers increased from 3.0% in 1975-1982 to 42.0%-43.8% in 1987-1988. Of the 317 TMP-resistant Shigella isolates identified during 1975-1988, 175 (55%) collected in 1985-1987 and in 1988 were tested further. Almost all (98%) were highly resistant to TMP, suggesting a plasmid-mediated origin. The type I dihydrofolate reductase (DHFR) gene was detected in 85% of the isolates studied. Twenty-three percent of the type I DHFR-positive isolates failed to hybridize with a probe detecting only Tn7-derived sequences, suggesting that the type I DHFR gene may occur independently of transposon Tn7. Four of the five Shigella species isolated from travelers to Sri Lanka hybridized with the probe for type V DHFR gene, implying a local distribution of the type V DHFR gene. The type II and type III DHFR genes were not found among the isolates studied. Only 12% of the TMP-resistant Shigella isolates failed to hybridize with any of the DHFR gene probes used.

DNA Probes↗
PubMed1978

Isolation of a small DNA fragment carrying the gene for a dihydrofolate reductase from a trimethoprim resistance factor.

DNA fragments of the R factor R388 which renders E. coli resistant to trimethoprim by inducing a trimethoprim resistant dihydrofolate reductase (Amyes and Smith, 1974) were inserted into plasmids and screened for the expression of the trimethoprim resistance gene. By means of a two step deletion procedure a 1770 bp EcoRI/BamH1 fragment was isolated which conferred drug resistance and which was found to induce the synthesis of the same dihydrofolate reductase as the parental R factor. Gene dosage experiments indicated that the induction was due to the presence of a dihydrofolate reductase structural gene on the 1770 bp fragment. The gene could be assigned to a segment which was less than 1200 bp long. The 1770 bp fragment and a recombinant plasmid consisting of pSF2124 and part of R388 were mapped with several restriction nucleases. The R factor induced enzyme was partially purified from a strain carrying a multicopy recombinant plasmid into which the 1770 bp fragment was inserted and which induced high levels of dihydrofolate reductase. The enzyme was found to be stable at 100 degrees. Some aspects of the synthesis of dihydrofolate reductase are discussed.

DNA, Bacterial↗
PubMed1985

A follow-up survey of transferable, plasmid-encoded trimethoprim resistance in a general hospital (1975-1983).

Urinary isolates of bacteria resistant to trimethoprim were collected at the Whittington Hospital, London, during five three-monthly periods during 1975, 1977, 1979, 1981, and 1983. Seventy-six transferable trimethorpim-resistant isolates so obtained were examined for their antibiotic resistance patterns, trimethoprim resistance (TpR) levels and plasmid molecular weights. Overall between 1975 and 1983 the frequency of transferable TpR rose from 10% to 40% of trimethoprim-resistant isolates, caused mainly by an increasing number of Escherichia coli isolates which cotransferred antibiotic resistance to trimethoprim, streptomycin and spectinomycin. From 1975-1979 the rise in the frequency of transferable TpR was due to a gradual increase amongst in-patient isolates but since 1979 transferable TpR rose rapidly due to a ten-fold increase in out-patient isolates.

Cross Infection↗
PubMed1992

The distribution of the DHFR genes in trimethoprim-resistant urinary tract isolates from Taiwan.

Between July 1987 and June 1989, 1054 urinary isolates of enterobacteria from Kaohsiung, Taiwan were studied for their trimethoprim resistance. Trimethoprim resistance was defined as MIC greater than 4 micrograms/ml and high-level resistance by MIC greater than 1000 micrograms/ml. The incidence of trimethoprim resistance increased from 33.6% in 1987 to 42.1% in 1989. Among the resistant strains studied, 90% were resistant to high levels of trimethoprim. An increase in the proportion of resistant strains (33.9-46.3%) exhibiting high-level non-transferable trimethoprim resistance was noted. The distribution of the dihydrofolate reductase (DHFR) genes by colony hybridization in 374 trimethoprim-resistant isolates revealed the presence of type I and type V DHFR genes in most of these isolates (45.4% and 10.4% respectively). Type I was predominant in Escherichia coli whereas type V was frequently seen in Enterobacter spp. None showed homology with the type II and type III DHFR probe DNA. In addition, transposon Tn7 was present in 7.8% of 374 trimethoprim-resistant enterobacteria.

DNA Transposable Elements↗