PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Drug Resistance, Multiple”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 145 records · Page 8Linked to original sources
PubMed2002

Molecular characterization of multiple-drug-resistant Mycobacterium tuberculosis isolates from northwestern Russia and analysis of rifampin resistance using RNA/RNA mismatch analysis as compared to the line probe assay and sequencing of the rpoB gene.

This investigation evaluated the potential of RNA/RNA mismatch analysis for the detection of rifampin resistance among 38 multiple-drug-resistant (MDR) isolates of Mycobacterium tuberculosis from northwestern Russia. The results obtained were compared with a commercialized line probe assay and rpoB sequencing, and the genetic diversity of the isolates was also investigated in parallel using spoligotyping and variable number of tandem DNA repeats (VNTR). The mismatch analysis revealed 3 distinct RNA cleavage profiles permitting the subdivision of the strains into mutation groups 1 to 3, the most common being group 1 (28 of 38 isolates) that contained a majority of strains with a TCG531>TTG (Ser->Leu) mutation, followed by group 2 (6 of 38 isolates) characterized by different mutations in the codon CAC526 (His), and group 3 (4 of 38 isolates), all characterized by a GAC516(Asp) mutation. Spoligotyping revealed the Beijing type to be the most prevalent among mismatch group 1 (24 out of 28 strains), suggesting that the most frequent rpoB mutation among the Beijing family in our setting was TCG531 >TTG (Ser->Leu). All the Beijing type isolates were also characterized by a unique VNTR pattern made up of exact tandem repeats (ETR)-A to E of 42435. We conclude that the Beijing genotype constitutes the major family of MDR-TB isolates currently circulating in northwestern Russia, and that the in-house RNA/RNA mismatch analysis may be successfully used for rapid and reliable diagnosis of rifampin-resistant tuberculosis in this setting.

Amino Acid Sequence↗
PubMed2006

Multiple-drug-resistant bacteria in patients with severe acute exacerbation of chronic obstructive pulmonary disease: Prevalence, risk factors, and outcome.

OBJECTIVE: To determine prevalence, risk factors, and effect on outcome of multiple-drug-resistant (MDR) bacteria in patients with severe acute exacerbation of chronic obstructive pulmonary disease. DESIGN: Prospective, observational, cohort study. SETTING: Thirty-bed medical intensive care unit (ICU) in a university hospital. METHODS: All chronic obstructive pulmonary disease patients with acute exacerbation who required intubation and mechanical ventilation for >48 hrs were eligible during a 4-yr period. Patients with pneumonia or other causes of acute respiratory failure were not eligible. In all patients, quantitative tracheal aspirate was performed at ICU admission (positive at 10 colony-forming units [cfu]/mL). MDR bacteria were defined as methicillin-resistant Staphylococcus aureus, ceftazidime- or imipenem-resistant Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia, and extended-spectrum beta-lactamase-producing Gram-negative bacilli. All patients received empirical antibiotic treatment at ICU admission. Univariate and multivariate analyses were used to determine variables associated with MDR bacteria and variables associated with ICU mortality. RESULTS: A total of 857 patients were included, and 304 bacteria were isolated (>/=10 cfu/mL) in 260 patients (30%), including 75 MDR bacteria (24%) in 69 patients (8%). When patients with MDR bacteria were compared with patients without MDR bacteria, previous antimicrobial treatment (odds ratio [OR], 2.4; 95% confidence interval [95% CI], 1.2-4.7; p = .013) and previous intubation (OR, 31; 95% CI, 12-82; p < .001) were independently associated with MDR bacteria. When patients with bacteria other than MDR or patients with no bacteria were used as a reference group, these risk factors were still independently associated with MDR bacteria. Although ICU mortality rate was higher in patients with MDR bacteria than in patients without MDR bacteria (44% vs. 25%; p = .001; OR, 2.3; 95% CI, 1.4-3.8), MDR bacteria were not independently associated with ICU mortality. Inappropriate initial antibiotic treatment (88% vs. 5%; p = <.001; OR, 6.7; 95% CI, 3.8-12) and ventilator-associated pneumonia (23% vs. 5%; p = <.001; OR, 1.3; 95% CI, 1-1.8) rates were significantly higher in patients with MDR bacteria than in patients with bacteria other than MDR. Inappropriate initial antibiotic treatment was independently associated with increased ICU mortality (OR, 7.1; 95% CI, 1.9-30; p = .003). CONCLUSION: MDR bacteria are common in patients with acute exacerbation of chronic obstructive pulmonary disease requiring intubation and mechanical ventilation. Previous antimicrobial treatment and previous intubation are independent risk factors for MDR bacteria. Although MDR bacteria are not independently associated with ICU mortality, inappropriate initial antibiotic treatment is an independent risk factor for ICU mortality in these patients. Further studies are needed to determine whether broad-spectrum antibiotic treatment is cost-effective in these patients.

Acute Disease↗
PubMed2005

An epidemiological study of the susceptibility and frequency of multiple-drug-resistant strains of Pseudomonas aeruginosa isolated at medical institutes nationwide in Japan.

The susceptibility of 3233 strains of Pseudomonas aeruginosa, isolated primarily in 2001, as agents of infection at 37 medical institutes with various specialties in seven regions of Japan (ranging from Hokkaido to Kyushu/Okinawa), to 18 antipseudomonal agents known to be active against P. aeruginosa was evaluated, in accordance with the National Committee for Clinical Laboratory Standards (NCCLS) guidelines. Of the 18 antipseudomonal agents, including some combinations of beta-lactamase inhibitors and antibacterial agents, ciprofloxacin had the lowest minimum inhibitory concentration (MIC)(50) (0.25 microg/ml) against P. aeruginosa, followed by meropenem, with an MIC(50) of 0.5 microg/ml. The MIC(50) of 7 of the examined antibacterial agents (ceftazidime, cefozopran, imipenem, biapenem, gentamicin, tobramycin, and levofloxacin) was between 1 and 2 microg/ml. Among the antipseudomonal agents tested, tobramycin showed the lowest MIC(90) (2 microg/ml), which was not significantly different from its MIC(50) (1 microg/ml). The MIC(90) of the other antibacterial agents examined ranged from 8 to 64 microg/ml and more. The susceptibility of the 3233 strains to the 12 antibacterial agents covered by the NCCLS guidelines was determined according to the standard method of the NCCLS guidelines. The frequency of strains resistant to meropenem, gentamicin, or tobramycin was relatively low (7.5%-8.3%). The frequency of strains showing intermediate to severe resistance to tobramycin was particularly low (8.0%). The frequency of strains resistant to aztreonam, imipenem, or levofloxacin was 16.7%-19.0%, about twice as high as the frequency of strains resistant to tobramycin. The susceptibility pattern of the 3233 strains (isolated from seven regions of Japan) to five antibacterial agents (ceftazidime, piperacillin, imipenem, gentamicin, and ciprofloxacin) was evaluated in relation to the regions from which they were isolated. The MIC(50) values of these antibacterial agents did not differ significantly among the regions. However, the MIC(90) values of ceftazidime and gentamicin were higher for strains isolated from the Kansai region than for strains isolated from other regions. The MIC(90) of ciprofloxacin was higher for strains isolated from the Tohoku, Kansai, and Kyushu/Okinawa regions than for strains isolated from other regions. Of the 3233 strains, 89 were classified as multiple-drug-resistant (imipenem, gentamicin, and ciprofloxacin) strains. Of these 89 strains, 42 were isolated from urine, 17 from sputum or pharyngeal mucus, 13 from pus, 8 from blood, 1 from cerebrospinal fluid, and 8 from other specimens. The frequency of multiple-drug-resistant strains was higher among strains isolated from the Tohoku and Kansai regions than in strains isolated from other regions.

Cerebrospinal Fluid↗
PubMed1986

Lysosomotropic agents reverse multiple drug resistance in human cancer cells.

Chloroquine, a well-known lysosomotropic amine, partially reversed the resistance of multi-drug-resistant KB carcinoma cells to adriamycin, daunomycin, vincristine, vinblastine and actinomycin D. Other lysosomotropic amines, propranolol, atropine, amantadine and nicotine, also restored the sensitivity of multi-drug-resistant cells to the anticancer drugs. The increased rate of accumulation of [3H] daunomycin by chloroquine was more prominent in the resistant KB-ChR-24 cells than in the parental KB cells. Chloroquine inhibited the efflux of daunomycin from the resistant cells. Circumvention of multiple drug resistance in human KB carcinoma cells by the agents is discussed in relation to lysosomal function.

Antineoplastic Agents↗
PubMed2001

Vibrio cholerae O1 outbreak isolates in Mozambique and South Africa in 1998 are multiple-drug resistant, contain the SXT element and the aadA2 gene located on class 1 integrons.

The characteristics of Vibrio cholerae O1 biotype El Tor, serotype Ogawa isolates from outbreaks of cholera in 1998 amongst migrant workers in the South African provinces of Gauteng and Mpumalanga, on the border of Mozambique, are reported. The isolates seem to have originated from the same clone since they are of two closely related BglI ribotypes. These ribotypes had a high similarity to ribotypes of V. cholerae O1 recently found in three South-east Asian countries. Isolates were resistant to furazolidone, streptomycin, sulfamethoxazole, trimethoprim and tetracycline. Only two isolates contained plasmids of 54 and 63 kb in size. PCR and DNA sequencing revealed that the chromosomally located resistance determinants present included an aadA2 gene cassette contained in a class 1 integron; the SXT element, which is a transposon-like element containing resistance genes; and the tetA gene. A co-transfer of chromosomal closely located genes encoding the SXT element and tetA was shown by mating experiments, PCR and pulsed-field gel electrophoresis analyses. Our study shows for the first time that multiple-resistant V. cholerae O1 isolates containing class 1 integrons and the SXT element were responsible for cholera outbreaks in Southern Africa. Studies are needed to determine the spread of this multiple-resistant O1 strain and further genetic details of the association of the SXT element, tetA and class 1 integrons, including their means of transfer.

Anti-Bacterial Agents↗
PubMed2006

Foscarnet salvage therapy for patients with late-stage HIV disease and multiple drug resistance.

OBJECTIVE: To evaluate the efficacy of foscarnet on HIV infection in patients with late-stage HIV disease and multiple drug resistance. METHODS: Three drugs experienced patients with plasma viral load (pVL) > 50,000 copies/ml and CD4+ T-cell counts < 100/mm3 were eligible for this open-label, single-arm, add-on pilot study. Foscarnet induction therapy consisted of 5 g intravenously twice daily for 6 weeks, in addition to a stable antiretroviral regimen. Patients with at least 1 log10 decrease in pVL at week 6 (W6), were given foscarnet 5 g intravenously twice daily on two consecutive days each week. Primary endpoint was the virological response rate at W6. RESULTS: Eleven patients were enrolled with a median baseline pVL at 5.16 log10 copies/ml, median CD4+ T-cell count at 10/mm3 and median number of mutations of 9, 2 and 12 associated with resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs and protease inhibitors, respectively. One patient discontinued foscarnet at W2 because of renal toxicity. In an intent-to-treat analysis, the median change in pVL from baseline was -1.99 log10 copies/ml at W2 and -1.79 log10 copies/ml at W6. Eight out of eleven patients had a fall in pVL of at least 1 log10 at W6, and six started maintenance therapy. The median fall in pVL after 12 weeks of maintenance therapy was -0.85 log10 copies/ml in the four patients who reached W12, and the median increase of CD4+ T-cell count was 60/mm3. CONCLUSION: In patients with HIV mutations conferring resistance to all antiretroviral drug classes, foscarnet markedly reduced plasma HIV load and improved immunological status.

Adult↗
PubMed1995

Relationship between enterotoxicity and multiple drug resistance in Aeromonas spp.

One hundred forty-seven isolates of Aeromonas spp., including 54 from diarrhoeal patients and 93 from the environmental sources, were examined for drug sensitivity and enterotoxin production. One hundred and fifteen (78%) isolates that included all A. hydrophila, 60% of A. sobria and 89% of A. caviae showed resistance to one or more antibiotic(s). Most (65%) of the resistant isolates caused fluid accumulation in rabbit ileal loops, of these 57% were A. hydrophila, 69% of A. sobria and 65% A. caviae, whereas only a few drug-sensitive isolates did so. Multiple drug-resistant isolates caused comparatively more fluid accumulation than the drug-sensitive isolates. Furthermore, significant difference of ileal fluid accumulation was observed with the increase in the number of resistance markers. This study suggests that there is some association between multiple drug resistance and enterotoxicity of Aeromonas strains, regardless of their source of isolation and species.

Adult↗
PubMedDate not supplied

Identification of insertion mutations in HIV-1 reverse transcriptase causing multiple drug resistance to nucleoside analogue reverse transcriptase inhibitors.

OBJECTIVE: A novel 2-amino acid insertion between codons 69 and 70 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) which confers multiple drug resistance has recently been reported. Independently, we have identified similar insertion mutations in Japanese hemophiliacs and attempted to analyze their emergence in conjunction with therapy regimens and their contribution to drug resistance using recombinant technology. METHODS: The plasma and peripheral blood mononuclear cells (PBMCs) of 348 HIV-1-infected hemophiliacs were screened for HIV-1 RT mutations relevant to nucleoside analogue inhibitors and isolating viruses. Contribution of each insertion to drug resistance was studied by introducing the mutations into a T-cell line-tropic NL4-3 infectious clone and testing the drug susceptibilities of the recovered virus. RESULTS: Insertion of the 2-amino acid residue was found in 4 of the 348 cases and was strongly associated with prolonged chemotherapy with zidovudine (AZT) and didanosine (ddI). The virus isolated from 1 of the 4 cases possessed the same insertion. Characterization of these virus and the recombinant NL4-3 with the insertion strongly suggested that the insertion caused resistance not only to AZT and ddI but also to lamivudine (3TC) and zalcitabine (ddC). CONCLUSION: A 2-amino acid insertion between codons 69 and 70 of RT was detected in 4 of 348 (1.1%) Japanese hemophiliacs and was found to be associated with multiple drug resistance to nucleoside analogue RT inhibitors.

Amino Acid Sequence↗
PubMed2005

Mosaic structure of a multiple-drug-resistant, conjugative plasmid from Campylobacter jejuni.

Partial sequence analysis of a tet(O) plasmid from a multiple-drug-resistant clinical isolate of Campylobacter jejuni revealed 10 genes or pseudogenes encoding different aminoglycoside inactivating enzymes, transposase-like genes, and multiple unknown genes from a variety of pathogenic and commensal bacteria. The plasmid could be mobilized by a P incompatibility group plasmid into Escherichia coli, where it apparently integrated into the chromosome and expressed high-level resistance to multiple aminoglycoside antibiotics. This work provides new information about both the nature of drug resistance in C. jejuni and the ability of C. jejuni to exchange genes with other bacterial species.

Anti-Bacterial Agents↗
PubMed2006

Isolation and characterization of VceC gain-of-function mutants that can function with the AcrAB multiple-drug-resistant efflux pump of Escherichia coli.

VceC is the outer membrane component of the major facilitator (MF) VceAB-VceC multiple-drug-resistant (MDR) efflux pump of Vibrio cholerae. TolC is the outer membrane component of the resistance-nodulation-division AcrAB-TolC efflux pump of Escherichia coli. Although these proteins share little amino acid sequence identity, their crystal structures can be readily superimposed upon one another. In this study, we have asked if TolC and VceC are interchangeable for the functioning of the AcrAB and VceAB pumps. We have found that TolC can replace VceC to form a functional VceAB-TolC MDR pump, but VceC cannot replace TolC to form a functional AcrAB-VceC pump. However, we have been able to isolate gain-of-function (gof) VceC mutants which can functionally interface with AcrAB. These mutations map to four different amino acids located at the periplasmic tip of VceC. Chemical cross-linkage experiments indicate that both wild-type and gof mutant VceC can physically interact with the AcrAB complex, suggesting that these gof mutations are not affecting the recruitment of VceC to the AcrAB complex but rather its ability to functionally interface with the AcrAB pump.

Anti-Bacterial Agents↗
PubMed1984

Acquisition of multiple drug resistance by CCRF-CEM cells selected for different degrees of resistance to vincristine.

We studied the acquisition of multiple drug resistance to several "natural product" drugs by cultured human leukemic lymphoblasts selected for increasing resistance to vincristine (VCR). Three apparent types of cross-resistance patterns could be distinguished: specific, pleiotropic, and mixed. Cross-resistance to vindesine developed in parallel with VCR resistance, appearing at the lowest levels of VCR resistance (approximately fivefold). Vinblastine resistance did not become noticeable until VCR resistance was higher (approximately equal to 50-100-fold). Cross-resistance resistance to three other tubulin-binding agents developed in a different pattern, however. While cross-resistance to maytansine was seen in cells of intermediate (approximately equal to 50-fold) resistance to VCR, colchicine cross-resistance occurred only in cells that were highly resistant to VCR (approximately equal to 500-fold). Even at the highest level of VCR resistance (approximately equal to 600-fold), complete sensitivity to podophyllotoxin was retained. Conversely, cross-resistance to the epipodophyllotoxins , teniposide and etoposide, semisynthetic derivatives of podophyllotoxin, was seen in cells that were greater than 50-fold resistant to VCR. The same pattern obtained for the anthracyclines, doxorubicin and daunorubicin. We conclude that resistance to low concentrations of VCR does not uniformly confer cross-resistance to other classes of natural product drugs.

Animals↗
PubMed1996

Multiple drug resistance and intermediate filaments.

One major obstacle to the successful treatment of epithelial derived tumors, such as breast and prostate carcinoma, is the presence of a multiple drug resistance phenotype. The drug resistance which is observed in growing epithelial derived cancer cells could either be an intrinsic, selected and/or an acquired characteristic. A survey of the survival data from several laboratories suggests that epithelial derived tumor cells, which have never been challenged with damaging agents, are in some cases 10 to 2,000 times more resistant to various chemotherapeutic agents as compared to hematopoietic cell lines. An intrinsic characteristic of epithelial cells is their resistance to the lethal effects of multiple types of damaging agents. A major feature of epithelial derived tumors is the expression of the intermediate filament type proteins known as cytokeratin. The simplest cytokeratin combination, cytokeratin 8 and 18, is a major cytoplasmic element within the cells of epithelial derived tumors. Earlier work showed that cytokeratin could be modified by mitoxantrone, a chemotherapeutic agent used in the treatment of breast cancer. Increasing data indicates that the intrinsic drug resistance phenotype is due in part to the presence of continued expression of the cytokeratin 8 and 18. The cytokeratin dependent drug resistance (C-MDR) has been observed in two different cell types that were engineered to contain cytokeratin 8 and 18 expression. The cytokeratin monomers are known to self assemble into intermediate filament networks as shown by numerous basic studies. Experiments using transfected cell lines which are unable to assemble networks indicated that C-MDR does not depend upon the formation of an intermediate filament network. Selection of cytokeratin network defective tumor cells did not increase their sensitivity to chemotherapeutic agents. These data are interesting since it suggests that the C-MDR phenotype is not dependent upon the structural nature (i.e. network forming ability) of the cytokeratin. Our current working hypothesis is that the interaction of the damaging agent with cytokeratin may initiate signaling response(s) for cell survival.

Animals↗
PubMedDate not supplied

Multiple drug resistant non typhoidal Salmonella spp associated with acute diarrheal disease.

Rectal swabs/stool specimens from 115 children (0-5 years) suffering with acute diarrhea were screened for non typhoidal salmonella species. 7 (6%) patients were found to be positive for non typhoidal salmonella. 4 (3.47%) were positive for S. paratyphi B and 3 (2.6%) were positive for S. typhimurium. Multidrug resistance was seen in 57 percent of the strains. All strains were sensitive to Ciprofloxacin. All strains were resistant to Ampicillin followed by Ciprofloxacin. All strains were resistant to Ampicillin followed by Gentamycin (43%), Kanamycin (43%), Tetracycline (43%), Streptomycin (28.5%) and Chloramphenicol (28.5%).

Acute Disease↗
PubMed1995

Analysis of second-site mutations that suppress the multiple drug resistance phenotype of the yeast PDR1-7 allele.

The yeast PDR1 locus encodes a member of the C6 zinc cluster family of transcriptional regulatory proteins. Among the targets of PDR1 is the yeast PDR5 locus. The product of this gene is a member of the ATP-binding cassette (ABC) transmembrane protein family and plays a major role in inhibitor efflux. Mutations in PDR1 affect the relative level of PDR5 transcript and can therefore result in increased or decreased drug resistance. We isolated three second-site suppressors of a PDR1-7 semidominant hyper-resistant mutation. These mutants were drug hypersensitive, as compared with isogenic controls. Two of the three mutations contained alterations in a putative DNA-binding domain. Significantly, the mutant proteins exhibited reduced DNA-binding capacity.

ATP-Binding Cassette Transporters↗
PubMed2005

Multiple drug resistance, antimutagenesis and anticarcinogenesis.

Many cells are protected from excess levels of exogenous chemicals, including mutagens and carcinogens as well as pharmaceutical agents, by being actively extruded through the action of one or more of a series of ATP-binding cassette drug transporter proteins. Those known to be important in humans are the multidrug resistance proteins (P-glycoproteins, encoded by the mdr1 and 3 genes), multidrug-resistance-associated proteins (MRP1-7) and the breast cancer resistance protein (BCRP). These proteins have overlapping but distinct cellular locations and substrate specificities, and jointly govern the likelihood of penetration or distribution of a given mutagen or carcinogen into various tissues including the brain, testis, ovaries and fetus. Thus, they can affect the absorption, distribution and excretion of mutagens and carcinogens, as well as of their metabolites and conjugates, in most cases acting to prevent or reduce mutagenesis or carcinogenesis. However, because ABC transporters may limit the success of chemotherapy, there has been a considerable effort by the pharmaceutical industry to develop inhibitors of this transport process, and these are increasing in use. In general, the mutagenicity of many chemicals may be increased at the cellular levels by the action of these inhibitors, while the altered absorption characteristics favour greater uptake into the body. Thus, in many cases, such inhibitors may counter the antimutagenic and anticarcinogenic effect of the multidrug resistance mechanisms. There are exceptions, however. An increasing number of single nucleotide polymorphisms in multidrug resistance genes are being identified in humans, and may account for many of the significant differences in inter-individual susceptibility to exogenous and endogenous mutagenic and carcinogenic insults.

ATP Binding Cassette Transporter, Subfamily B, Mem↗