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Susceptibility of inbred rat strains to experimental thyroiditis: quantitation of thyroglobulin-binding cells and assessment of T-cell function in susceptible and non-susceptible strains.

Ten inbred strains of rats were immunized with crude homologous thyroglobulin emulsified in Freund's complete adjuvant in order to investigate strain susceptibility to the induction of both thyroiditis and antibody to thyroglobulin. Two strains (LH and AUG) were found to be extremely susceptible and had 100% incidence of thyroid lesions which in general varied from moderate to very severe (mean index of pathology+/-SE, 2-5+/-0-2 and 2-1+/-0-4 respectively). One other strain (HL) also had 100% incidence of lesions but there were consistently mild in character (1-1+/-0-1). Two strains (DA and SD) were variable, with thyroid change varying from negative to severe. Three strains (LEW, WAG and PVG/c) had occasional lesions and the remaining two strains (AS and CAM) showed no thyroid change. Four strains (LH, AUG, HL and DA) consistently produced good antibody responses to thyroglobulin (mean titres+/-SE 7-3+/-0-3, 9-5+/-0-4, 6-9+/-0-3 and 6-6+/-0-5 respectively). In contrast WAG and CAM rats failed to develop autoantibody and the responses of AS, PVG/c and SD strain rats were quite variable. Although the autoantibody response generally correlated well with the presence of thyroiditis in a particular strain, LEW, AS and PVG/c rats often had good antibody levels with minimal thyroid lesions. Females of the most susceptible strains (LH and AUG) were found to have significantly more severe thyroid lesions and higher antibody titres to thyroglobulin than males. The most susceptible strains were all found to be of the Ag-B5 major histocompatibility genotype whilst the least susceptible were of the Ag-B2 genotype. However, wide interstrain variability was noted within the Ag-B5 genotype particularly with respect to the induction and extent of thyroid lesions. It was not found possible to relate the divergence in susceptibility between rat strains of Ag-B5 and Ag-B2 genotypes to differences in respective numbers of thyroglobulin-binding cells within the circulation of the non-immunized animal. Similarly, there were no differences in response between a susceptible (LH) and non-susceptible (CAM) strain to the phytomitogens PHA and Con A.

Animals

Paramyxovirus-avian cell relationship: discrepant impact of 6-azauridine on virus production by susceptible and less susceptible cells.

The replication of mumps virus in susceptible chicken embryonic heart cells was escalated by daily treatment of cultures with 6-azauridine (6-AU). On the other hand, virus production by less susceptible liver cells was depressed by 6-AU. The population of infected susceptible cells was not increased, but the release of virus by infected susceptible cells was enhanced 20-fold by 10 mug of 6-AU per ml. Less susceptible cells, which incorporated less ribonucleic acid and protein precursor than susceptible cells, sustained a constant level of viral release during 6-AU treatment; however, the number of infected less susceptible cells underwent substantial decline.

Animals

Caries susceptibility in inbred mouse strains and inheritance patterns in F1 and backcross (N2) progeny from strains with high and low caries susceptibility.

We studied dental caries susceptibility in various inbred mice strains infected with Streptococcus mutans and the inheritance pattern in the F1 and the N2 backcross animals. A high caries score was observed in four laboratory strains, BALB/cAJcl, C57BL/6NJcl, C57BL/10Slc and DBA/2NJcl. Three strains, C3H/HeNJcl, AKR/JSlc and CBA/JNCrj, showed less caries. Males of strain C57BL/10Slc (mean caries score = 112.2) and females of strain C3H/HeNJcl (mean caries score = 24.0) were chosen for examinations of the inheritance of the caries susceptibility. The mean caries score in (C57BL/10Slc x C3H/HeNJcl) F1 hybrids was 98.4, demonstrating that F1 progenies were susceptible. A number of N2 mice were obtained by mating the F1 male and the C3H/HeNJcl female. The caries scores of these N2 male mice had an extensive range, from 14 to 194. Assuming that a caries score over 74 (median of the scores between C57BL/10Slc and C3H/HeNJcl) belonged to the highly caries-susceptible group, N2 mice could be divided into groups with low or high caries susceptibility. Furthermore, the effect of nu/nu mutation on caries susceptibility in mice was also examined.

Analysis of Variance

Susceptibilities of zidovudine-susceptible and -resistant human immunodeficiency virus isolates to antiviral agents determined by using a quantitative plaque reduction assay.

Conventional assays based on infection of T-cell lymphoblastoid lines with tissue culture-adapted strains of human immunodeficiency virus (HIV) are well established and have been used successfully to discover potent inhibitors of HIV replication. In this report we show that such assays are not easily applied to testing the susceptibilities of clinical HIV isolates to inhibitors because of differences in replication rates and cytotoxicity, thus demonstrating that conventional HIV assays should be used with caution when the zidovudine susceptibility of clinical isolates is assessed. An assay based on plaque reduction in CD4+ HeLa cell monolayers was validated by determining susceptibilities of HIV to a large number of inhibitors in this system. In general, 50% inhibitory doses for HIV type 1 and 2 strains derived from plaque reduction data were in good agreement with susceptibility data obtained by using conventional assays with T-cell lines. The susceptibilities of previously identified zidovudine-resistant HIV isolates to a large group of inhibitors, including nonucleosides, such as interferons and soluble CD4, were tested by using a plaque reduction assay in CD4+ HeLa cells. Surprisingly, an extremely narrow range of cross resistance was observed; cross resistance was limited to nucleoside analogs containing a 3'-azido group. These data point the way to the use of combinations of inhibitors to delay the appearance of drug resistance.

Antiviral Agents

Susceptibilities of penicillin-susceptible and -resistant strains of Streptococcus pneumoniae to RP 59500, vancomycin, erythromycin, PD 131628, sparfloxacin, temafloxacin, win 57273, ofloxacin, and ciprofloxacin.

The MICs of four new quinolones, sparfloxacin (AT-4140, CI-978), PD 131628 (the active form of the prodrug CI-990), temafloxacin, and Win 57273, compared with those of ciprofloxacin and ofloxacin were tested against 53 penicillin-susceptible, 35 penicillin intermediate-resistant, and 51 penicillin-resistant pneumococci. Susceptibility to RP 59500, a new streptogramin, was also tested and compared with those to the quinolones, erythromycin, and vancomycin. All MICs were determined by a standardized agar dilution method by using Mueller-Hinton agar supplemented with sheep blood. Quinolone, vancomycin, and RP 59500 susceptibilities were not affected by susceptibility or resistance to penicillin. For Win 57273, the MICs for 50% (MIC50) and 90% (MIC90) of strains tested were 0.015 and 0.03 micrograms/ml, respectively. MIC50S of both sparfloxacin and PD 131628 were 0.25 micrograms/ml, and MIC90S were 0.5 micrograms/ml. The MIC50 of temafloxacin was 0.5 micrograms/ml, and the MIC90 was 1.0 micrograms/ml. By comparison, ofloxacin and ciprofloxacin both yielded MIC50S of 1.0 micrograms/ml and MIC90s of 2.0 micrograms/ml. RP 59500 yielded an MIC50 of 0.5 microgram/ml and an MIC90 of 1.0 microgram/ml and was only 1 doubling dilution less active against 17 erythromycin-resistant strains. Vancomycin was active against all strains (MIC50, 0.25 microgram/ml; MIC90, 0.5 microgram/ml). All four experimental quinolones as well as RP 59500 show promise for therapy of infections with penicillin-resistant and -susceptible pneumococci.

Anti-Infective Agents

In-vitro susceptibility of cefoperazone-susceptible and -resistant gram-negative rods to cefoperazone plus sulbactam, other beta-lactams, aminoglycosides and quinolone.

We compared the in-vitro activity of cefoperazone-sulbactam (2:1), other beta-lactams, amino-glycosides and ciprofloxacin against cefoperazone-susceptible and -resistant nosocomial gram-negative bacilli. Resistant isolates including Pseudomonas aeruginosa were susceptible to cefoperazone-sulbactam; the susceptible isolates had modestly increased susceptibility to the combination. Sulbactam, by itself, was poorly active. Among others tested, ciprofloxacin and imipenem were the most active. No inoculum effect was seen with cefoperazone-sulbactam and this drug combination had a prolonged post-antibiotic effect. Cefoperazone-sulbactam is an attractive candidate for evaluation in the treatment of nosocomial infections due to aerobic gram-negative bacilli.

4-Quinolones

Susceptibility of anaerobic bacteria to sulfamethoxazole/trimethoprim and routine susceptibility testing.

The minimal inhibitory concentrations (MICs) of sulfamethoxazole and trimethoprim against 144 strains of obligately anaerobic bacteria were determined on Diagnostic Sensitivity Test agar (Oxoid) or in prereduced Diagnostic Sensitivity Test broth, both supplemented with sodium pyruvate (1 mg/ml), hemin (5 mug/ml), and vitamin K(1) (1 mug/ml). Fifty-eight percent of the strains were susceptible to sulfamethoxazole alone (MIC </= 16 mug/ml), only 12% were susceptible to trimethoprim alone (MIC </= 1 mug/ml), and 85% were susceptible to the combination of sulfamethoxazole plus trimethoprim (MIC </= 16 mug/ml) at a ratio of 19:1. All 45 strains of the Bacteroides fragilis group were susceptible to the combination. Synergy of the combination was often observed by a checkerboard MIC determination of 123 strains, usually most markedly when the ratio of the two components was near 1:1. However, there was also synergism at the ratio of sulfamethoxazole to trimethoprim of 16:1 in 61 (53.5%) of the 114 strains that could be evaluated for synergistic activity. When the strains were tested by the broth-disk test proposed by Wilkins and Thiel, modified by using prereduced Diagnostic Sensitivity Test broth instead of brain heart infusion broth and by using a smaller inoculum, there was over 90% correlation with the MICs. Poor results were found when the broth-disk tests were performed in brain heart infusion broth. There was very poor correlation between inhibition zone diameters by an agar diffusion method and MICs.

Bacteria

[Susceptibilities of clinical bacterial isolates to antimicrobial agents. A study mainly focused on imipenem. Reported by the Research Group for Testing Imipenem Susceptibility on Clinical Isolates].

This study was conducted to investigate susceptibilities of clinical bacterial isolates to imipenem (IPM) and other antibacterial agents at 64 hospital laboratories throughout Japan from September to December of 1988. In this study, identification and susceptibility testing were carried out at each laboratory and the tests were performed according to the disk dilution method recommended by NCCLS in which susceptibilities are classified into "S", "MS", "I" and "R". IPM showed markedly high in vitro activities against Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Enterococcus faecalis, Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter cloacae, Serratia marcescens, Salmonella spp., Citrobacter freundii, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia rettgeri, Providencia stuartii, Acinetobacter calcoaceticus, Moraxella (Branhamella) catarrhalis, Alcaligenes spp., Peptococcus spp./Peptostreptococcus spp., Bacteroides fragilis and Bacteroides spp. IPM also had strong activities against Achromobacter xylosoxidans and Pseudomonas aeruginosa, but less active against Flavobacterium spp., E. faecium, coagulase-negative staphylococci (CNS), Staphylococcus aureus and Pseudomonas cepacia. In a study in which activities of IPM against bacteria isolated from different clinical sources were compared, differences in susceptibilities were observed among S. aureus, CNS, A. calcoaceticus and P. aeruginosa, but such differences were not apparent among S. pneumoniae, E. faecalis, H. influenzae, E. coli, K. pneumoniae, E. cloacae, C. freundii, S. marcescens or P. mirabilis.

Bacteria

Discrepancies in isoniazid susceptibility profiles: Bactec MGIT 960-resistant but GenoType MTBDRplus-susceptible Mycobacterium tuberculosis strains in Hunan, China.

UNLABELLED: Discordant drug susceptibility testing (DST) results between the Bactec MGIT 960 system (MGIT) and the GenoType MTBDRplus assay (MTBDRplus) for isoniazid (INH) complicate clinical decision-making. In this study, we performed minimum inhibitory concentration (MIC) assays and whole-genome sequencing (WGS) on 53 Mycobacterium tuberculosis strains identified as INH-resistant by MGIT but INH-susceptible by MTBDRplus. The variants conferring INH resistance were evaluated by the WHO mutation catalogue. Our results showed that only five strains carried variants classified as "associated with resistance" (Group 1/2), including katG Trp39STOP, katG Ser315Asn, inhA -154G>A, and inhA Ser94Ala. In addition, 44 strains carried 70 variants classified as "Group 3: Uncertain significance" across nine genes, including katG, ahpC, inhA, Rv0010c, Rv1129c, Rv2752c, mshA, dnaA, and Rv1258c. The remaining four strains carried no variants (Groups 1-3) linked to INH resistance. No significant difference in the prevalence of high-level INH resistance was observed between lineage 2 and lineage 4 strains (&#x3c7;&#xb2; = 0.232, P = 0.630). Our findings indicate that the variants classified as "uncertain significance" may be the main genetic determinants causing discordant results, highlighting their associations with INH resistance that need to be further investigated. IMPORTANCE: This study addresses a critical challenge in drug susceptibility testing (DST): the discrepancies in DST results for isoniazid (INH) between the Bactec MGIT 960 system and the GenoType MTBDRplus assay. These discordant results significantly complicate treatment decisions, potentially leading to suboptimal patient outcomes. Using MIC assays and WGS on 53 clinical Mycobacterium tuberculosis strains, we provide valuable insights into the genetic basis of INH resistance. Our findings showed that only a small fraction of strains carried variants definitively linked to INH resistance, while a larger number harbored variants of uncertain significance across multiple genes, underscoring the complexity of INH resistance mechanisms. This study highlights the urgent need to refine our understanding of these "Group 3: uncertain significance" variants, as they appear to be a primary driver of the discrepancies. Additionally, this study emphasizes the importance of integrating advanced sequencing tools into DST to improve the accuracy of INH resistance detection.

Isoniazid

Characterization of Staphylococcus aureus isolates with decreased susceptibility to vancomycin and teicoplanin: isolation and purification of a constitutively produced protein associated with decreased susceptibility.

"Derivative isolates" with 4- to 8-fold and 8- to 16-fold increases in MICs of vancomycin and teicoplanin, respectively, were selected from 2 susceptible clinical isolates of Staphylococcus aureus by serial incubation in low-level vancomycin. A protein of approximately 39 kDa was demonstrable in the cytoplasmic fraction and occasionally in the membrane fraction by SDS-PAGE of both derivatives. This protein was purified by DEAE chromatography, preparative SDS-PAGE, and electroelution. Derivative bacteria were larger on transmission electron microscopy, had thicker cell walls, and had changes in colony morphology on solid media. Further evidence for cell wall reorganization included loss of phage and capsular typing, decreased susceptibility to lysostaphin/lysozyme killing, and changes in condition for detection of optimal coagulase activity. The mechanism of decreased susceptibility to glycopeptide antibiotics among S. aureus derivative isolates is uncertain. The production of the approximately 39-kDa cytoplasmic protein and cell wall reorganization may mediate changed affinity of glycopeptide-peptidoglycan binding or impairment of glycopeptide access to its cell wall target.

Bacterial Proteins

Effect of age of non-skin tissues on susceptibility of skin grafts to 7,12-dimethylbenz[alpha]anthracene (DMBA) carcinogenesis in BALB/c mice, and effect of age of skin graft on susceptibility of surrounding recipient skin to DMBA.

The influence of age-dependent alterations in non-skin tissues on chemical carcinogen-induced skin papilloma development was studied by treatment with 7,12-dimethylbenz[alpha]anthracene (DMBA) of 4-month-old skin grafts sewed onto 4- and 20-month-old syngeneic recipients. Skin of 4- and 20-month-old BALB/c female mice differed in susceptibility to DMBA carcinogenesis, but the 4-month-old grafts showed the same papilloma incidence independent of the age of the recipient mice. In a different experiment, the influence of age of skin grafts on papilloma development on DMBA-treated recipient skin was studied. Fourteen- and 26-month-old skin grafts were carried by 14-month-old recipients. Grafts of those two ages are known to differ in susceptibility to DMBA carcinogenesis, but no effect of the grafts on papilloma development on DMBA-treated recipients was detectable. It was concluded that certain age-dependent differences in skin susceptibility to chemical carcinogens are solely a reflection of alterations in the skin at the site of carcinogen treatment.

9,10-Dimethyl-1,2-benzanthracene

Paradoxical effect of Tween 80 between the susceptibility to rifampicin and streptomycin and the susceptibility to ethambutol and sulfadimethoxine in the Mycobacterium avium-Mycobacterium intracellulare complex.

The susceptibility to rifampicin and streptomycin of the Mycobacterium avium-Mycobacterium intracellulare complex was augmented by the addition of Tween 80 into 7H10 agar medium with OADC, whereas the susceptibility to ethambutol and sulfadimethoxine was either not changed or reduced by the addition of Tween 80. In 7H10 agar medium without OADC, however, susceptibilities to both rifampicin and sulfadimethoxine were reduced by the addition of Tween 80 to the medium. A number of hypotheses are made to explain these phenomena.

Antitubercular Agents

A tape-recorded test of hypnotic susceptibility for screening headache patients: a feasibility study of the Harvard Group Scale of Hypnotic Susceptibility, Form A.

A study to examine the feasibility of using the Harvard Group Scale of Hypnotic Susceptibility, Form A (HGSHS) as a screening instrument was undertaken at an inpatient headache treatment program. Nine patients diagnosed with chronic daily headache and drug rebound were administered the HGSHS. Analysis of the results showed no significant difference in hypnotic susceptibility when headache patients were compared to a control group. After taking the HGSHS, three of the five subjects who had headache at the time of testing reported a 25% reduction in pain, one was unchanged, and one reported a 13% increase in pain. The results obtained did not suggest a correlation between level of hypnotic susceptibility and reduction of headache.

Adult

[Susceptibilities of clinical bacterial isolates to antimicrobial agents, 1989. A study mainly focused on imipenem. The Research Group for Testing Imipenem Susceptibilities of Clinical Isolates].

We investigated susceptibilities of clinical bacterial isolates to imipenem (IPM) and other antimicrobial agents at hospital laboratories throughout Japan from September to December of 1989. The susceptibility testing was carried out according to the 1-dilution or 3-dilution disc technique in which susceptibilities are classified into 4 grades: (+++), (++), (+) and (-). IPM showed markedly high in vitro activities against Streptococcus pneumoniae, Neisseria gonorrhoeae, Moraxella catarrhalis, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter freundii, Acinetobacter calcoaceticus, Bacteroides fragilis and had rather strong activities against Enterococcus faecalis, Haemophilus influenzae, Serratia marcescens, Proteus mirabilis, Morganella morganii, Pseudomonas aeruginosa and Achromobacter xylosoxidans, but was less active to Staphylococcus aureus, coagulase-negative staphylococci and Xanthomonas maltophilia. IPM has been found to have activities superior to those of other antibiotics tested against E. faecalis, E. cloacae, C. freundii, S. marcescens, P. aeruginosa and B. fragilis. No antibiotics tested showed good activities against MRSA except minocycline.

Bacteria

[Susceptibilities of clinical bacterial isolates to antimicrobial agents. A study mainly focused on imipenem. Research Group for Testing Imipenem Susceptibility on Clinical Isolates].

We investigated susceptibilities of clinical bacterial isolates to imipenem (IPM) and other antimicrobial agents at 459 hospital laboratories throughout Japan from September to December of 1988. In this study, identification and susceptibility testing were performed at each hospital laboratory and the tests were carried out according to the 1-dilution or 3-dilution disc technique in which susceptibilities are classified into 4 grades: , ++, + and -. IPM had significantly high activity against Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Neisseria gonorrhoeae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter cloacae, Salmonella spp., Citrobacter freundii, Proteus mirabilis, Providencia rettgeri, Acinetobacter calcoaceticus, Moraxella catarrhalis, Alcaligenes spp., Peptococcus spp./Peptostreptococcus spp., Bacteroides fragilis and Bacteroides spp. and should slightly lower activities on coagulase-negative staphylococci (CNS), Enterococcus faecalis, Haemophilus influenzae, Serratia marcescens, Proteus vulgaris, Providencia stuartii and Pseudomonas aeruginosa than on the above mentioned bacteria. In a comparative study on activities of IPM against bacteria from different clinical sources, no remarkable differences were found due to different sources among S. pneumoniae, E. faecalis, H. influenzae, E. coli, K. pneumoniae, E. cloacae, C. freundii, P. mirabilis or A. calcoaceticus, whereas slight differences were found among Staphylococcus aureus, CNS, S. marcescens and P. aeruginosa.

Anti-Bacterial Agents

[Susceptibilities of uropathogenic bacteria to ampicillin, cefazolin, cefmetazole and gentamicin. Nine-year survey of changing patterns of susceptibilities].

We analyzed antibiotic susceptibilities of urinary isolates of Escherichia coli, Klebsiella spp., Proteus mirabilis, and Indole (+) Proteus group to ampicillin (ABPC), cefazolin (CEZ), cefmetazole (CMZ) and gentamicin (GM) in 69 laboratories in 1988 and also studied changing patterns of susceptibilities from 1980 to 1988. Minimal inhibitory concentrations were determined using the agar dilution method (MUELLER-HINTON agar, BBL) with inoculation of 10(6) cfu/ml of bacteria. Ninety to 99% of the strains of E. coli, Klebsiella spp. and P. mirabilis were inhibited at a concentration of 6.25 micrograms/ml of CEZ and CMZ and of 1.56 micrograms/ml of GM. Approximately 80% of the strains of Indole (+) Proteus group were inhibited at concentrations of 6.25 micrograms/ml of CMZ and of 1.56 micrograms/ml of GM. However, resistance to ABPC and CEZ was high, with 83% and 81% of the strains being not inhibited at a concentration of 50 micrograms/ml of ABPC and CEZ, respectively. No significant changes in susceptibilities of the 4 bacteria to the above 4 antibiotics were observed over the 9 year period. No increase was found in the incidence of the resistant strains of the 4 bacteria to CMZ and GM, nor of E. coli and Klebsiella spp. to CEZ.

Ampicillin

Antimicrobial susceptibility patterns of Haemophilus isolates from children in eleven developing nations. BOSTID Haemophilus Susceptibility Study Group.

The antimicrobial susceptibilities of 426 isolates of Haemophilus species, which were collected as part of a worldwide study of the etiology of acute respiratory disease in children in selected developing countries, were determined. Eleven antibiotics were tested using the recently described Haemophilus Test Medium. There was a low prevalence of antibiotic resistance; 6% of strains were resistant to ampicillin, and 1.6% were resistant to chloramphenicol. Strains resistant to both ampicillin and chloramphenicol were recovered only from Thailand. Susceptibility to penicillin G was also determined; the minimum inhibitory concentrations for penicillin and ampicillin were concordant within one 2-fold dilution in 97% of the isolates. Thus, Haemophilus isolates were as susceptible to penicillin G as they were to ampicillin, and penicillin resistance was infrequent overall. These data provide support for the current protocols for the management of acute respiratory infections in children in developing countries, in which penicillin G is a first-line agent.

Anti-Bacterial Agents

Resistance and susceptibility of mice to bacterial infection: course of listeriosis in resistant or susceptible mice.

Resistance and susceptibility to Listeria monocytogenes in mice was found to be related to (i) the innate ability of the nonimmune macrophages to kill or inhibit the growth of the organism during the first 24 to 48 h after infection, and (ii) the time of onset of acquired cell-mediated resistance. Resistant C57Bl/6 mice were 10 times more efficient than susceptible BALB/c mice at suppressing the early growth of Listeria in the liver. Furthermore, the onset of acquired immunity occurred 24 to 48 h earlier in C57Bl/6 than in BALB/c mice. Acquired immunity was measured by (i) fall in bacterial numbers in spleen and livers of infected mice (ii) adoptive transfer of immunity to normal mice by using spleen cells from infected mice, (iii) delayed-type hypersensitivity skin testing, and (iv) uptake of tritiated thymidine by lymphocytes in the spleen.

Animals