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PubMed2004

Comparison of susceptibility test methods to detect penicillin susceptibility in Streptococcus pneumoniae isolates.

The increasing prevalence of penicillin-resistant Streptococuus pneumoniae urges for fast and accurate susceptibility testing methods. This study evaluated the comparability of three commonly used techniques; disk diffusion, E-test and agar dilution, to detect penicillin susceptibility in clinical isolates of S. pneumoniae. Fifty pneumococcal isolates, obtained from patients at the University of Malaya Medical Centre, were selected to include both penicillin-susceptible strains and those that had decreased susceptibility (resistant and intermediate) to penicillin. The minimum inhibitory concentration (MIC) values of penicillin to serve as the reference was determined by the agar dilution method in which, based on the MIC breakpoints recommended by the National Committee for Clinical Laboratory Standards (NCCLS), 27 strains had decreased susceptibility to penicillin with 17 strains resistant and 10 intermediate. Comparing to the agar dilution method, oxacillin disk diffusion test detected all strains with decreased penicillin susceptibility as such while E-test showed a close agreement of susceptibility (92%) of the isolates to penicillin. This confirmed that oxacillin is a good screening test for S. pneumoniae isolates with decreased susceptibility to penicillin while E-test is very reliable for rapid and accurate detection of penicillin susceptibility.

Anti-Bacterial Agents↗
PubMed1998

Selection of susceptible and refractory lines of Glossina morsitans centralis for Trypanosoma congolense infection and their susceptibility to different pathogenic Trypanosoma species.

In a single generation of selection, two lines of Glossina morsitans centralis were established that differed significantly in susceptibility to Trypanosoma congolense clone IL 1180. Reciprocal crosses demonstrated that susceptibility was a maternally inherited trait. Differences between the lines, to all phases of the trypanosome infection, were maintained for eight generations, whereas differences in susceptibility to midgut infections were maintained for twenty-eight generations. Thereafter, the lines did not differ in susceptibility to Trypanosoma congolense IL 1180. Susceptibility to infections with Trypanosoma congolense IL 1180 was only a weak predictor of susceptibility to T. congolense clones IL 13-E3 and K60/1, as well as clone T. brucei brucei STIB 247-L. However, the susceptible and refractory lines displayed these phenotypes when tested with Trypanosoma vivax, indicating that the factors that affect susceptibility to trypanosomes are expressed both within and outside the midgut.

Animals↗
PubMed1986

Extrachromosomal inheritance of susceptibility to trypanosome infection in tsetse flies. II. Susceptibility of selected lines of Glossina morsitans morsitans to different stocks and species of trypanosome.

Two lines of Glossina m. morsitans, selected for susceptibility and refractoriness to infection with a single stock of Trypanosoma congolense, have now been shown to be susceptible or refractory to different stocks of T. congolense and, also, to different stocks of T. b. brucei and T. b. gambiense. The mean midgut infection rates of the susceptible line obtained in different experiments with T. congolense, T. b. brucei and T. b. gambiense were, respectively, 66%, 56% and 55%; the corresponding mature (hypopharynx or salivary gland) infection rates were 37%, 23% and 0%. The highest mature infection rates obtained in individual experiments with susceptible flies were 65% (T. congolense) and 40% (T. b. brucei). Mean T. congolense and T. b. brucei midgut infection rates obtained with the refractory line were 29% and 33% respectively, the mature infection rates being 12% and 7%, all significantly lower than the corresponding rates in the susceptible line. Development of midgut infections in susceptible flies appears to take place irrespective of trypanosome stock or form. There is some evidence to suggest that higher infection rates can be obtained with flies infected and maintained on mammals rather than on in vitro feeding systems. Susceptible flies matured a significantly greater proportion of their midgut T. congolense and T. b. brucei infections than did the refractory line, which suggests that maturation of infections is influenced by the susceptibility status of the fly. However, the apparent inability of these flies to develop mature infections of a major T. b. gambiense genetic grouping suggests that maturation of infections established in the midgut is a phenomenon primarily associated with trypanosome genotype.

Animals↗
PubMed1994

Use of cefotaxime or ceftazidime susceptibility tests for predicting susceptibility of Enterobacteriaceae and Pseudomonas aeruginosa.

To determine if susceptibility to aztreonam could be predicted from cefotaxime or ceftazidime disc diffusion testing, 919 Enterobacteriaceae and 187 Pseudomonas aeruginosa clinical strains were studied. The correlation coefficient between the diameters of inhibition zones was 0.9 for cefotaxime versus aztreonam and ceftazidime versus aztreonam comparisons in Enterobacteriaceae and 0.75 for ceftazidime versus aztreonam comparison in P. aeruginosa. For 99% of the Enterobacteriaceae, there was no risk in predicting susceptibility to aztreonam on the basis of cefotaxime or ceftazidime susceptibility tests. To minimize the risk of the remaining 1% of the strains being erroneously classified as susceptible to aztreonam, ceftoaxime should be tested in preference to ceftazidime, and the production of extended-spectrum beta-lactamases should be tested for using the cefotaxime-clavulanate disc synergy test. For P. aeruginosa strains, susceptibility to aztreonam could be accurately predicted from ceftazidime susceptibility tests for ticarcillin susceptible strains, but for ticarcillin resistant strains, susceptibility to aztreonam should be tested.

Aztreonam↗
PubMed1993

[Diagnosis of malignant hyperthermia susceptibility. 1. The significance of in vitro susceptibility tests].

UNLABELLED: Molecular genetic findings indicate genetic heterogeneity in susceptibility to malignant hyperthermia (MH). At present the in vitro contracture test (IVCT) is still the most reliable diagnostic procedure for MH susceptibility. It must be performed in a standardized fashion. METHODS. We investigated 350 patients (233 children and 117 adults) using the protocol of the European MH Group for the IVCT. The test results were classified as susceptible to MH (MHS), non-susceptible to MH (MHS), non-susceptible to MH (MHN) and equivocal (MHE), with an abnormal caffeine result designated MHEc and an abnormal halothane result designated MHEh. Reasons for the IVCT were a positive family history for MH susceptibility (n = 94), a MH reaction (n = 157), creatine kinase elevation unknown aetiology (n = 53) and different neuromuscular diseases (NMD, n = 46). Physical, neurological and laboratory work-up included serum enzymes, nerve conduction studies, electromyography and muscle biopsy evaluated by different techniques. Thirty-one children and 11 adults were MHS, while 152 children and 80 adults were MHN. MHE findings were obtained in 50 children and 26 adults. While the MHS and MHN groups are diagnostically safe, the equivocal group is not, with possible false-negative or false-positive interpretation. The high number of MHE findings most probably is explained by the high proportion of patients with NMD (53% of the children, 69% of the adults). RESULTS. In a group of 18 boys with Duchenne or Becker muscular dystrophy, ranging in age from 1.5 to 24 years, the IVCT results were twice MHS, once MHE, and MHN in the remaining 15 cases. In seven other boys with Duchenne or Becker muscular dystrophy, proven by molecular techniques, there were anaesthetic complications with MH-like symptoms. After administration of trigger substances, five out of the seven suffered a cardiac arrest, two of whom died. In the surviving five boys the IVCT results were three times MHN, once MHE and once MHS. Most probably these boys suffered from effects of succinylcholine, possibly potentiated by other trigger substances. The adverse cardiac reactions are attributed to triggered rhabdomyolysis with associated hyperkalemia but not a primary hereditary disposition to MH. CONCLUSION: In patients with NMD, MHS and MHE test results do not indicate a hereditary, heterogeneous disposition to MH; the majority will be caused by a secondary induced disturbance of calcium homoeostasis in the diseased muscle cells. These results do, however, indicate the following: (1) Patients with NMD exposed to trigger substances are at higher risk than the general population for MH-like episodes, including sudden death. (2) NMD therefore should be diagnosed as early as possible and patients should not be exposed to trigger substances when alternatives are at hand. (3) Diagnostic procedures in patients having suffered an MH-like episode should include IVCT and special investigations to exclude or substantiate other NMD. The work-up may be changed if a family member is properly classified as MH susceptible. (4) In patients with known NMD there is no indication for performing IVCT, since the results may even be misleading.

Adult↗
PubMed2001

A procedure for evaluation and documentation of susceptibility test methods using the susceptibility of Klebsiella pneumoniae to ciprofloxacin as a model.

A new procedure for the evaluation and documentation of susceptibility test methods is described. To illustrate the procedure, four basically different susceptibility test methods were examined in a routine laboratory. The test parameter detection of decreased susceptibility to ciprofloxacin (breakpoint MIC 0.25 mg/L) among 94 selected isolates of Klebsiella pneumoniae was used. In addition to comparison of frequency histograms and regression analysis, the accuracies of the susceptibility test methods were determined using the receiver operating characteristic procedure. For each of the methods, the sensitivity (SN), specificity (SP), positive predictive value (PV+) and negative predictive value (PV-) for detection of decreased susceptibility to ciprofloxacin were calculated and plotted against a range of ciprofloxacin inhibition zones determined by the various susceptibility test methods or MICs determined by the Etest (Etest MICs). The results illustrate the accuracy and the robustness of the methods, which can be used to expose the need for training and instruction of laboratory staff. It becomes possible to optimize and justify the choice of inhibition zone breakpoints or Etest MIC breakpoints according to the SN and SP of the method employed. Furthermore, the consequences of adjustments of these breakpoints on the PV+ and PV- can be analysed and related to different clinical and epidemiological situations. We believe that our approach can be used as a model for the evaluation and documentation of susceptibility test methods in general.

Anti-Infective Agents↗
PubMed1973

Susceptibility of Bacteroides fragilis to six antibiotics determined by standardized antimicrobial disc susceptibility testing.

The susceptibility of 100 or more strains of Bacteroides fragilis to six antibiotics was determined by standardized agar dilution and disc diffusion tests. Good correlation of results of the two methods was obtained with chloramphenicol, clindamycin, lincomycin, penicillin, and vancomycin. Correlation of results with erythromycin was not as good. A great deal of overlapping of zone diameters among strains classed as susceptible, intermediate, and resistant occurred with both erythromycin and lincomycin, making interpretation of disc diffusion tests difficult. All strains tested were susceptible to chloramphenicol; 94% were susceptible to clindamycin at concentrations readily achieved with ordinary dosage, and all strains were inhibited by 6.2 mug/ml, a level which is achieved with somewhat more intensive therapy. Only 7% were shown to be susceptible to erythromycin and 13% to lincomycin under the conditions of our testing procedure. Only a small percentage of the strains were susceptible to penicillin, and none was susceptible to vancomycin.

Anti-Bacterial Agents↗
PubMed1997

Reappraisal of the antimicrobial susceptibilities of Chryseobacterium and Flavobacterium species and methods for reliable susceptibility testing.

Several Flavobacterium species, comprising a heterogeneous group of gram-negative bacilli that are capable of causing opportunistic infections in humans, have recently been reclassified as Chryseobacterium or Myroides species. Intrinsically resistant to a number of antibiotics, these organisms have been reported to be susceptible to vancomycin and certain other drugs that are normally active against gram-positive bacteria. By using the National Committee for Clinical Laboratory Standards (NCCLS) broth microdilution procedure, 58 clinical isolates of former flavobacteria (36 Chryseobacterium meningosepticum isolates, 11 C. indologenes isolates, 3 C. gleum isolates, 4 unspeciated former members of Flavobacterium group IIb, and 4 Myroides odoratum isolates) were tested with 23 antibiotics, including conventional and investigational agents. In addition, the broth microdilution results were compared to those generated by agar dilution, E-test, and disk diffusion for vancomycin and piperacillin-tazobactam. Compared to the NCCLS microdilution results, there were 7.1 and 17.9% very major errors with piperacillin-tazobactam by agar dilution and E-test, respectively. In addition, there were from 12.1 to 48.3% minor errors with both procedures with vancomycin and piperacillin-tazobactam. The very major and minor error rates were unacceptably high with disk testing of piperacillin-tazobactam; the use of enterococcal vancomycin disk breakpoints (zone diameter of > or =17 mm = susceptible) resulted in >20% minor errors but only one very major error. All of the isolates were susceptible to minocycline; over 90% were susceptible to sparfloxacin, levofloxacin, and clinafloxacin; and 88% were susceptible to rifampin. None was susceptible to vancomycin. When Chryseobacterium or Myroides species are isolated from serious infections, susceptibility testing by broth microdilution should be performed and therapy should be guided by those results.

Anti-Bacterial Agents↗
PubMed1975

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↗
PubMed2004

Accumulation of genes for susceptibility to rust fungi for which barley is nearly a nonhost results in two barley lines with extreme multiple susceptibility.

Nonhost resistance is the most common type of resistance in plants. Understanding the factors that make plants susceptible or resistant may help to achieve durably effective resistance in crop plants. Screening of 109 barley (Hordeum vulgare L.) accessions in the seedling stage indicated that barley is a complete nonhost to most of the heterologous rust fungi studied, while it showed an intermediate status with respect to Puccinia triticina, P. hordei-murini, P. hordei-secalini, P. graminis f. sp. lolii and P. coronata ff. spp. avenae and holci. Accessions that were susceptible to a heterologous rust in the seedling stage were much more or completely resistant at adult plant stage. Differential interaction between barley accessions and heterologous rust fungi was found, suggesting the existence of rust-species-specific resistance. In particular, many landrace accessions from Ethiopia and Asia, and naked-seeded accessions, tended to be susceptible to several heterologous rusts, suggesting that some resistance genes in barley are effective against more than one heterologous rust fungal species. Some barley accessions had race-specific resistance against P. hordei-murini. We accumulated genes for susceptibility to P. triticina and P. hordei-murini in two genotypes called SusPtrit and SusPmur, respectively. In the seedling stage, these accessions were as susceptible as the host species to the target rusts. They also showed unusual susceptibility to other heterologous rusts. These two lines are a valuable asset to further experimental work on the genetics of resistance to heterologous rust fungi.

Basidiomycota↗
PubMed1997

Do non-insulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM) share genetic susceptibility loci? An analysis of putative IDDM susceptibility regions in familial NIDDM.

Non-insulin-dependent diabetes mellitus (NIDDM) has been viewed as genetically and physiologically distinct from insulin-dependent diabetes mellitus (IDDM), yet many of the recently suggested IDDM susceptibility loci are likely to increase the risk of diabetes through nonautoimmune mechanisms. To test the hypothesis that the IDDM susceptibility loci include important NIDDM susceptibility loci, we tested the linkage of 14 putative susceptibility regions with NIDDM among families and sibling pairs of Northern European descent. All regions were tested with highly informative microsatellite (simple tandem repeat) polymorphisms in up to 166 affected individuals from 42 families using both parametric and nonparametric methods (149 pairs for sibling pair analyses). We found no evidence for linkage to the majority of loci, including loci that appeared to be linked to IDDM in more than one study. We report some evidence for shared susceptibility for regions on chromosomes 1, 2, and 6. The best evidence based on multilocus affected pedigree member (APM) analysis of markers near D1S191 suggested linkage at P value .0001. This region has not yet been confirmed as an IDDM locus, and our analyses could represent a false-positive result. The role of these three regions will only be clarified by testing in additional families. In combination with other investigations in our laboratory for chromosome 11 susceptibility regions, our data generally do not provide convincing evidence that IDDM and NIDDM share common genetic factors among families of Northern European descent with ascertainment of two or more NIDDM siblings.

Adult↗
PubMed2005

Genetic control of susceptibility to Candida albicans in susceptible A/J and resistant C57BL/6J mice.

The importance of host factors in determining susceptibility to systemic Candida albicans infections is evident in both humans and mice. We have used a mouse model to study the genetic basis of susceptibility, using the inbred strains A/J and C57BL/6J, which are susceptible and resistant, respectively, based on different parameters of the response to infection. To identify genes responsible for this differential host response, brain and kidney fungal load were measured in 128 [A/J x C57BL/6J] F(2) mice 48 h after infection with 5 x 10(4) C. albicans blastospores. Segregation analysis in this informative population identified complement component 5 (C5/Hc) as the major gene responsible for this differential susceptibility (LOD of 22.7 for kidney, 19.0 for brain), with a naturally occurring mutation that causes C5 deficiency leading to enhanced susceptibility. C5 was also found to control heart fungal load, survival time, and serum TNF-alpha levels during infection. Investigation of the response to C. albicans challenge in a series of AcB/BcA recombinant congenic strains validated the importance of C5 in determining the host response. However, the strains BcA67 and BcA72 showed discordant phenotypes with respect to their C5 status, suggesting additional complexity in the genetic control of the inter-strain difference in susceptibility observed in A/J and C57BL/6J following systemic infection with C. albicans.

Analysis of Variance↗
PubMed2000

Rubella susceptibility predicts measles susceptibility: implications for postpartum immunization.

Measles and mumps antibody titers were measured in 262 pregnant women who were either positive (n=128) or negative (n=134) for rubella antibodies. Susceptibility to measles and mumps was detected in 4.6% (12/262) and 7.6% (14/184) of the women, respectively. Of the rubella-susceptible group, 8.2% were also measles susceptible, whereas only 0.8% of the rubella-immune women were measles susceptible. Susceptibility to mumps was evenly divided between rubella-susceptible (7.8%) and rubella-immune (7.4%) groups.

Adult↗
PubMed1991

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↗
PubMedDate not supplied

[From prevalence to predictive values: considerations on the antimicrobial susceptibility testing dealing with change of susceptibility rates].

The aim of the study was to quantify the influence of the variation of the susceptibility prevalence (frequencies of susceptible, intermediate and resistant isolates) on the predictive value of antimicrobial susceptibility testing reports performed with disk diffusion method, under several scenarios of distinct susceptibility prevalence. Prevalence variation effect was assessed through a modeling approach that enabled to take into account the technical variability and to control prevalence through scenarios. Results show how the prevalence impacts on the disk diffusion performance with level of discrepancies varying with prevalence. The phenomenon may be quantitatively noteworthy for some antimicrobial agents considering the prevalence recorded with time or location, leading to lowered performances. For instance, with amoxicillin+clavulanic acid, predictive values of susceptible and resistant reports varied respectively from 70 to 96 and from 33 to 97 %. For a 18-mm diameter, the probability the isolate is truly susceptible varied from 16 to 73 % according to the prevalence tested. Characteristic of the prevalence effect are described and consequences on zone diameter breakpoint policy raised. They include to (i) reevaluate disk diffusion breakpoint consistency when the prevalence impact is noteworthy and (ii) estimate the consequences of an international harmonized breakpoint policy on prediction quality and appropriate patient management.

Bacterial Infections↗
PubMed2005

Behavioral characteristics of WAG/Rij rats susceptible and non-susceptible to audiogenic seizures.

Some rats of the WAG/Rij (Wistar Albino Glaxo from Rijswijk) and Wistar strain are susceptible for audiogenic (convulsive) seizures. In the present study, behavior of susceptible and non-susceptible rats from the WAG/Rij strain, genetically predisposed to absence epilepsy, and outbred Wistar strain, genetically not predisposed to absence epilepsy, was compared to assess the level of anxiety (in the open field, light-dark choice and elevated plus-maze tests) and the level of depression (in the sucrose consumption and forced swimming tests). Increased level of anxiety was found only in audiogenic susceptible rats both from WAG/Rij and Wistar strain, but increased level of depression was found only in WAG/Rij rats independently of their susceptibility to audiogenic seizures. The results suggest that enhanced level of depression in WAG/Rij strain rats is associated with absence epilepsy but enhanced level of anxiety with susceptibility to audiogenic seizures.

Analysis of Variance↗
PubMed2004

How does susceptibility prevalence impact on the performance of disk diffusion susceptibility testing?

Antimicrobial disk diffusion susceptibility testing, devoted in a clinical context to predicting whether an antibiotic regimen will be effective, should be evaluated through predictive values. This approach implies that the susceptibility prevalence (frequency of susceptible, intermediate, and resistant isolates) affects the predictive value of a result. We quantified the influence of the susceptibility prevalence variation on the disk diffusion method performance through a modeling approach. Simulations based on a resampling procedure from two distinct minimum inhibitory concentration/diameter data sets were performed. Experimental variability on minimum inhibitory concentration and diameters was taken into account in the simulations. Results show that the susceptibility prevalence impact depends on the antibiotic and may be significant when prevalence variation is high enough. Consequences of these results on zone diameter breakpoint determination policy are discussed. This implies that the following should be done: (i) consider more rigorously the susceptibility prevalence in studies dealing with zone diameter breakpoint determination and performance evaluation, (ii) re-evaluate disk diffusion breakpoint consistency when the weight of prevalence variation is noteworthy, (iii) estimate consequences of a breakpoint international consensus on prediction quality and appropriate patient management.

Agar↗