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PubMed2000

Carriage of penicillin-susceptible and non-susceptible pneumococci in healthy young children in Göteborg, Sweden.

OBJECTIVES: To study carriage of Streptococcus pneumoniae among healthy young children, determine the proportion of strains with decreased susceptibility to penicillin, and study possible risk factors for the carriage of penicillin-resistant strains. METHODS: Between February 1996 and February 1997, 620 healthy, 18-month-old children in Goteborg, Sweden were screened for carriage of S. pneumoniae with decreased susceptibility to penicillin. Nasopharyngeal samples were obtained from children visiting child health centres for routine health control. RESULTS: Streptococus pneumoniae was found in 322 samples and 18 strains (5.6%, CI95 3.4; 8.8) of all pneumococci showed decreased susceptibility to penicillin G with minimum inhibitory concentrations (MICs) ranging from 0.125 to 1.0 mg/l. The proportion of strains with decreased susceptibility was similar to that found in a laboratory-based material (6%), from the same geographical area and time period. A majority of the children with strains with decreased susceptibility to penicillin (n = 11) were not attending day-care centres. CONCLUSIONS: The prevalence of S. pneumoniae with reduced susceptibility to penicillin is still low in unselected healthy Swedish children.

Carrier State↗
PubMed1999

Antimicrobial susceptibility of coagulase-negative staphylococci and characterization of isolates with reduced susceptibility to glycopeptides.

The antimicrobial susceptibility of 239 coagulase-negative staphylococci (CNS) isolates consecutively collected from blood culture in patients admitted in a 600-bed teaching hospital was evaluated. The isolates were identified to the species level by conventional methods and the MicroScan Positive Combo Panel type 6 system, and their susceptibility to vancomycin, teicoplanin, and oxacillin were tested by agar dilution, disk diffusion, and MicroScan-WalkAway system. The species distribution was as follows: Staphylococcus epidermidis 120 (50.2%), S. hominis 29 (12.1%), S. haemolyticus 24 (10.0%), S. cohnii 14 (5.9%), and isolates from other CNS species 52 (21.8%). The percentage of resistance to oxacillin was 74.5% by agar dilution. The highest percentages of oxacillin resistance were found among S. haemolyticus (95.8%) and S. epidermidis (80.8%). Teicoplanin resistance (MIC > or = 32 micrograms/mL) was detected in five S. haemolyticus isolates, whereas intermediate resistance (MIC = 16 micrograms/mL) was detected in nine strains. These isolates with reduced susceptibility to teicoplanin were resistant to oxacillin, but remained susceptible to vancomycin (MIC < or = 4 micrograms/mL). Two isolates, one S. haemolyticus and one S. epidermidis, showed a vancomycin MIC of 8 micrograms/mL, and both MicroScan and disk diffusion methods classified these isolates as susceptible. Our results showed that glycopeptide resistance is emerging among CNS isolates in our institution and the disk diffusion method may not detect isolates with decreased susceptibility to these antimicrobial agents.

Adult↗
PubMed1985

Extrachromosomal inheritance of susceptibility to trypanosome infection in tsetse flies. I. Selection of susceptible and refractory lines of Glossina morsitans morsitans.

Differences in susceptibility to infection with Trypanosoma congolense between F1 families of Glossina morsitans morsitans indicated that susceptibility is maternally inherited in this species of tsetse fly. Twelve F1 families, six selected for susceptibility and six selected for refractoriness to infection, have been bred for up to 13 generations. The reciprocal differences demonstrated in the F1 generation persisted in these selected families over many generations, indicating that susceptibility/refractoriness to T. congolense infection is extrachromosomally inherited in G. m. morsitans. Repeated 'backcrossing' to males of the opposite strain showed that infection rates within families were independent of the contribution of the male parent. Susceptible families had a mean midgut infection rate of 76.9% and a mature (hypopharyngeal) infection rate of 47.9%. In the refractory families 88.9% of the flies failed to develop an infection, 11.1% had midgut infections and only 6.3% developed mature infections. Levels of midgut infection remained remarkably constant within families over generations, whether refractory or susceptible, while maturation rates varied between generations and between sexes. Males matured a significantly greater proportion of midgut infections than females in the susceptible families. It is suggested that the inheritance of susceptibility/refractoriness relates primarily to the establishment of midgut infections in G. m. morsitans, and that maturation of midgut infections is dependent upon environmental factors such as diet, and differences between sexes probably reflecting differences in rates of bloodmeal digestion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Comparison between Aspergillus fumigatus conidia and hyphae susceptibilities to amphotericin B, itraconazole, and voriconazole by use of the mold rapid susceptibility assay.

Although hyphae are the morphological form observed in tissue during invasive Aspergillus fumigatus infections, antifungal susceptibility testing for A. fumigatus utilizes conidial inocula. Previous studies have yielded conflicting results as to whether conidia adequately reflect antifungal susceptibility of hyphae, but the ease of handling and quantification of conidia have prompted their use in such assays. The mold rapid susceptibility assay, which utilizes a conidial inoculum (cRSA), was adapted as a novel method to assess the utility of conidial versus hyphal inocula (hRSA) to further evaluate the susceptibility of A. fumigatus conidia and hyphae to amphotericin B (AMB), itraconazole (ITC), and voriconazole (VRC). Conidial inocula were prepared as previously described for the cRSA and minimum inhibitory values (MIC) were determined. For the hRSA, microtiter test wells lacking antifungal drug were inoculated with a standardized conidial inoculum and incubated for 12 h at 35-37 degrees C to allow formation of hyphae. Following addition of antifungal drug and 48 h incubation at 35-37 degrees C, hRSA antifungal minimum inhibitory concentration (MIC) values were determined by analysing the pattern of residual glucose levels in hRSA test wells. hRSA MIC values of each strain were influenced by hyphal inoculum size, with increasing hyphal inoculum size corresponding to increased AMB, ITC and VRC MIC values. Comparisons between the hRSA and cRSA MIC values demonstrated insignificant differences in conidial and hyphal susceptibility to drug, thus justifying the use of either fungal form in RSA-based susceptibility testing of A. fumigatus isolates. The RSA may be adapted for use of similar testing of other invasive molds that predominate as hyphal forms in tissue.

Amphotericin B↗
PubMed1997

Development of interpretive breakpoints for antifungal susceptibility testing: conceptual framework and analysis of in vitro-in vivo correlation data for fluconazole, itraconazole, and candida infections. Subcommittee on Antifungal Susceptibility Testing of the National Committee for Clinical Laboratory Standards.

The availability of reproducible antifungal susceptibility testing methods now permits analysis of data correlating susceptibility in vitro with outcome in vivo in order to define interpretive breakpoints. In this paper, we have examined the conceptual framework underlying interpretation of antimicrobial susceptibility testing results and then used these ideas to drive analysis of data packages developed by the respective manufacturers that correlate fluconazole and itraconazole MICs with outcome of candidal infections. Tentative fluconazole interpretive breakpoints for MICs determined by the National Committee for Clinical Laboratory Standards' M27-T broth macrodilution methodology are proposed: isolates for which MICs are < or = 8 microg/mL are susceptible to fluconazole, whereas those for which MICs are > or = 64 microg/mL appear resistant. Isolates for which the MIC of fluconazole is 16-32 microg/mL are considered susceptible dependent upon dose (S-DD), on the basis of data indicating clinical response when > 100 mg of fluconazole per day is given. These breakpoints do not, however, apply to Candida krusei, as it is considered inherently resistant to fluconazole. Tentative interpretive MIC breakpoints for itraconazole apply only to mucosal candidal infections and are as follows: susceptible, < or = 0.125 microg/mL; S-DD, 0.25-0.5 microg/mL; and resistant, > or = 1.0 microg/mL. These tentative breakpoints are now open for public commentary.

Animals↗
PubMed1989

[Study on bacterial infection by the investigation of antimicrobial susceptibility of various clinical isolates. III. Comparison of drug susceptibility between the isolates from the materials of out- and in-patients, and among the isolates from the materials of different hospital units].

Antimicrobial agents susceptibility of 42, 940 strains of clinical isolates (from 1979 to 1986) were investigated and the data were analyzed on the basis of the sources of isolates; materials from in- and out-patients or from the different hospital units. Bacteria studied were limited to the species of which isolates were 100 or more during 1979 to 1986. The following results were obtained. i) When the antibiotic susceptibility of the isolates from the out-patient-materials were compared with that from the in-patient-materials, the following 13 bacterial species isolated from the former source were found to be more susceptible to antibiotics than that of the latter. These were S. aureus, S. epidermidis, E. coli, Citrobacter sp., Klebsiella sp., Serratia sp., P. vulgaris, P. rettgeri, M. morganii, P. aeruginosa, P. putida, S. sonnei and Salmonella sp.. ii) The frequency of isolation and their antibiotic susceptibility of S. aureus, Enterobacter sp. and P. aeruginosa from both the in- and out-patients were comparable through 1979. However, S. aureus isolated from the in-patient-materials tended to show increased antibiotic resistance since 1983. This is probably due to the frequent use of the 3rd generation cephalosporins. iii) Comparison of the antibiotic susceptibility of the isolates from the different hospital units showed that the resistant strains were more frequently isolated in the materials from the urology unit and the susceptible strains were more frequently isolated in the materials from the infectious diseases unit. iv) Antibiotic resistant S. aureus and P. aeruginosa increased abruptly since 1983 in the materials from the surgery and urology unit, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteria↗
PubMed1982

In vitro susceptibility of methicillin-resistant and methicillin-susceptible Staphylococcus aureus strains to N-formimidoyl thienamycin.

A total of 82 clinical isolates of methicillin-resistant Staphylococcus aureus and 21 isolates of methicillin-susceptible S. aureus were studied for in vitro susceptibility to N-forminidoyl thienamycin at incubation temperatures of 30 and 35 degrees C. The disk diffusion test results were correlated with the macrobroth dilution test by means of the error rate-bounded method of analysis. Both methicillin-susceptible and (to a lesser degree) methicillin-resistant strains were generally susceptible to the antibiotic as judged from their minimum inhibitory concentrations. The discrepancy between in vitro results obtained at 30 and at 35 degrees C was not very remarkable. However, tolerance of N-formimidoyl thienamycin was observed in 37% of methicillin-resistant strains and 24% of methicillin-susceptible strains at an incubation temperature of 30 degrees C; at 35 degrees C, the values were 54% (methicillin-resistant strains) and 14% (methicillin-susceptible strains).

Anti-Bacterial Agents↗
PubMed1986

Effects of growth of methicillin-resistant and -susceptible Staphylococcus aureus in the presence of beta-lactams on peptidoglycan structure and susceptibility to lytic enzymes.

Growth of methicillin-resistant Staphylococcus aureus DU4916 in the presence of methicillin yielded crude cell walls that showed an increased rate of autolysis and purified cell walls (PCW) and peptidoglycan (PG) that had increased susceptibilities to autolysin extracted with LiCl and to lysozyme. The PG of cells grown in the presence of methicillin had markedly decreased cross-linking and O acetylation. Growth of the methicillin-susceptible strain H in the presence of subinhibitory concentrations of cefoxitin, a specific inhibitor of penicillin-binding protein (PBP) 4, caused a substantial decrease in PG cross-linking and O acetylation and increased susceptibilities of PCW and PG to LiCl-extracted autolysin and to lysozyme. Strain DU4916 cells grown in the presence of methicillin did not show an increased rate of autolysis or an increased susceptibility to vancomycin- or D-cycloserine-induced lysis, even though their PG was hypo-cross-linked. This implies that the potential for increased autolysis is controlled in intact cells and that this regulation may be involved in the methicillin resistance phenomenon. Growth of the methicillin-susceptible strain DU4916S in the presence of methicillin yielded PCW and PG that showed small increases in susceptibilities to LiCl-extracted autolysin and to lysozyme and a small decrease in PG cross-linking. Comparison of the PBPs of a penicillinase-nonproducing derivative of strain DU4916 (DU4916-K7) with those of strain DU4916S in intact cells and isolated membranes revealed that PBPs 1 to 4 had similar high beta-lactam antibiotic affinities in both strains and identified an additional PBP, PBP2(1), with low beta-lactam affinity in the methicillin-resistant strain DU4916-K7. The low degree of cross-linking of PG in strain DU4916 cells grown with methicillin was probably due mainly to inhibition of the secondary cross-linking function of PBP 4.

Acetylation↗
PubMed2002

Prospective, multicenter surveillance study of Candida glabrata: fluconazole and itraconazole susceptibility profiles in bloodstream, invasive, and colonizing strains and differences between isolates from three urban teaching hospitals in New York City (Candida Susceptibility Trends Study, 1998 to 1999).

Since the 1990s, the substantial increase in the rate of Candida glabrata infections has become a serious problem. As most C. glabrata infections arise from the host's endogenous microflora, the present prospective, multicenter analysis included all clinical isolates associated with colonization and with systemic and hematogenous candidiasis. Among 347 C. glabrata isolates, the overall rates of resistance to fluconazole (MIC > or = 64 micro g/ml) and itraconazole (MIC > or = 1 micro g/ml) were 10.7 and 15.2%, respectively, although for half (n = 148) of the itraconazole-susceptible isolates the MICs (0.25 to 0.5 micro g/ml) were in the susceptible-dependent upon dose range. Fluconazole resistance was more common among C. glabrata isolates obtained from centers caring for patients with cancer (MICs at which 90% of isolates are inhibited [MIC(90)s] = 32 micro g/ml) or AIDS (MIC(90)s > 64 micro g/ml) than among C. glabrata isolates from a community-based university medical center (MIC(90)s = 16 micro g/ml) (P = 0.001). Thirty-three bloodstream isolates and those obtained from other body sites had similar in vitro susceptibility profiles. The fluconazole MIC(90)s (< or =16 micro g/ml) for C. glabrata yeast isolates from the gastrointestinal tract were lower than those (> or =64 micro g/ml) for C. glabrata isolates from respiratory and urinary tract samples (P = 0.01). A similar discrepancy for itraconazole was not significant (P > 0.5). We did not observe differences in fluconazole or itraconazole susceptibility profiles among C. glabrata isolates associated with either hematogenous dissemination or colonization. The significant discrepancy in antifungal susceptibility among C. glabrata organisms isolated from hospitals in the same geographic region emphasizes the significance of periodic susceptibility surveillance programs for individual institutions, especially those providing care to patients at risk.

Antifungal Agents↗
PubMed2001

Methicillin-resistant Staphylococcus aureus: comparison of susceptibility testing methods and analysis of mecA-positive susceptible strains.

Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for an increasing number of serious nosocomial and community-acquired infections. Phenotypic heterogeneous drug resistance (heteroresistance) to antistaphylococcal beta-lactams affects the results of susceptibility testing. The present study compared the MRSA-Screen latex agglutination test (Denka Seiken Co., Ltd., Tokyo, Japan) for detection of PBP 2a with agar dilution, the VITEK-1 and VITEK-2 systems (bioMérieux, St. Louis, Mo.), and the oxacillin agar screen test for detection of MRSA, with PCR for the mecA gene used as the "gold standard" assay. Analysis of 107 methicillin-susceptible S. aureus (MSSA) isolates and 203 MRSA isolates revealed that the MRSA-Screen latex agglutination test is superior to any single phenotype-based susceptibility testing method, with a sensitivity of 100% and a specificity of 99.1%. Only one isolate that lacked mecA was weakly positive by the MRSA-Screen latex agglutination test. This isolate was phenotypically susceptible to oxacillin and did not contain the mecA gene by Southern blot hybridization. The oxacillin agar screen test, the VITEK-1 system, the VITEK-2 system, and agar dilution showed sensitivities of 99.0, 99.0, 99.5, and 99%, respectively, and specificities of 98.1, 100, 97.2, and 100%, respectively. The differences in sensitivity or specificity were not statistically significant. Oxacillin bactericidal assays showed that mecA- and PBP 2a-positive S. aureus isolates that are susceptible to antistaphylococcal beta-lactams by conventional methods are functionally resistant to oxacillin. We conclude that the accuracy of the MRSA-Screen latex agglutination method for detection of PBP 2a approaches the accuracy of PCR and is more accurate than any susceptibility testing method used alone for the detection of MRSA.

Anti-Bacterial Agents↗
PubMed2000

Middle cerebral artery (MCA) susceptibility sign at susceptibility-based perfusion MR imaging: clinical importance and comparison with hyperdense MCA sign at CT.

PURPOSE: To describe the radiologic findings of susceptibility changes in acute middle cerebral artery (MCA) thromboembolism detected with three-dimensional (3D) susceptibility-based perfusion magnetic resonance (MR) imaging and to compare the detectability and clinical value of this sign with those of the hyperdense MCA sign at computed tomography (CT). MATERIALS AND METHODS: Twenty-three patients (mean age, 55 years) underwent CT and MR imaging within the first 6 hours after the onset of acute MCA stroke. The hyperdense MCA sign at CT and the presence of susceptibility changes in acute thromboembolism as depicted on T2*-weighted 3D perfusion MR images were assessed. The presence of each sign was correlated with clinical presentation. RESULTS: The sensitivity of the hyperdense MCA sign at CT was 54% (negative predictive value, 71%) compared with 82% (negative predictive value, 86%) for the susceptibility changes at MR imaging. There were no false-positive CT or MR readings. The presence of the MCA susceptibility sign correlated positively with the initial clinical presentation (chi(2) = 7.987, P =.009, Spearman rho = 0.589). However, neither of the signs was a predictor for clinical outcome in cases of spontaneous MCA stroke. CONCLUSION: In addition to the information traditionally provided with reconstructed perfusion parameter maps, 3D susceptibility-based perfusion MR images allow the identification of acute MCA thromboembolism with a sensitivity higher than that of CT.

Acute Disease↗
PubMedDate not supplied

Genetic variation between susceptible and non-susceptible snails to Schistosoma infection using random amplified polymorphic DNA analysis (RAPDs).

Susceptibility of snails to infection by certain trematodes and their suitability as hosts for continued development has been a bewildering problem in host-parasite relationships. The present work emphasizes our interest in snail genetics to determine what genes or gene products are specifically responsible for susceptibility of snails to infection. High molecular weight DNA was extracted from both susceptible and non-susceptible snails within the same species Biomphalaria tenagophila. RAPD was undertaken to distinguish between the two types of snails. Random primers (10 mers) were used to amplify the extracted DNA by the polymerase chain reaction (PCR) followed by polyacrylamide gel electrophoresis (PAGE) and silver staining. The results suggest that RAPD represents an efficient means of genome comparison, since many molecular markers were detected as genetic variations between susceptible and non-susceptible snails.

Animals↗
PubMedDate not supplied

[Antimicrobial susceptibility testing of bacteria isolated from animals: methods for in-vitro susceptibility testing and their suitability with regard to the generation of the most useful data for therapeutic applications].

In-vitro susceptibility testing provides valuable informations for choosing the most suitable antimicrobial agent for the control of bacterial infections in animals. Different diffusion and dilution methods, as conducted according to various approved performance standards, can be used to determine the in-vitro susceptibility of bacterial pathogens. In the present article, problems are discussed which arise from the use of different methods and the difficulty to interpret such results. While most approved performance standards were designed for testing of bacteria from human sources, the NCCLS document M31-A2 exclusively focusses on susceptibility testing of bacteria isolated from animals and--in contrast to all other standards--includes veterinary specific breakpoints for a number of antimicrobial agents used in veterinary medicine. Therefore, performance of in-vitro susceptibility testing of veterinary pathogens should follow the recommendations given in the NCCLS document M31-A2. The microdilution method is recommended as the method of choice for susceptibility testing. The result of a microdilution test is given as the minimum inhibitory concentration (MIC). This value provides a quantitative result which precisely indicates the degree of susceptibility of the tested bacterial strain and in return gives the veterinarian a clear guidance whether therapeutic intervention with the antibiotic in question will be successful.

Animals↗
PubMed1989

[Susceptibilities of clinical isolates to antibacterial agents. A study mainly focused on ofloxacin (the second report). Reported by the Research Group for Testing ofloxacin Susceptibility on Clinical Isolates].

Susceptibilities of various clinical isolates to ofloxacin (OFLX) and other antibacterial drugs were examined at 128 hospital laboratories in 36 prefectures throughout Japan between April, 1986 and March, 1987. The results were totalized with an emphasis mainly on OFLX and were compared with data obtained in the previous year. In this study, identification and susceptibility tests of the isolates were carried out at each hospital laboratory and the tests were performed according to the 1-dilution or 3-dilution disc method in which susceptibilities are classified into 4 grades: , ++, +, and -. Similarly to the study performed in the previous year, species showing susceptibilities to OFLX included Staphylococcus aureus (4,205 strains), Staphylococcus epidermidis (2,009 strains), Entercoccus faecalis (1,697 strains), Streptococcus pneumoniae (702 strains), Escherichia coli (4,097 strains), Klebsiella pneumoniae (1,375 strains), Enterobacter cloacae (762 strains), Enterobacter aerogenes (296 strains), Citrobacter freundii (406 strains), Proteus mirabilis (613 strains), Morganella morganii (320 strains), Serratia marcescens (869 strains), Haemophilus influenzae (1,282 strains), Pseudomonas aeruginosa (4,206 strains), Acinetobacter calcoaceticus (351 strains), Acinetobacter sp. (415 strains), and Campylobacter jejuni (151 strains). Neisseria gonorrhoeae (26 strains) were exceptional due to their smaller number this time than that of the previous year and only the susceptibility to OFLX was investigated with this species. As results, OFLX showed strong antibacterial activities (similar to the previous year) against S. aureus, S. epidermidis, N. gonorrhoeae, E. coli, K. pneumoniae, E. cloacae, E. aerogenes, C. freundii, P. mirabilis, M. morganii, H. influenzae, A. calcoaceticus, Acinetobacter sp., and C. jejuni. However, when these susceptibilities shown in the present study were compared to those obtained in the previous year, many species showed decreases in the occurrence of or increases in -, though they were rather small changes. The following species were not totalized in the previous year due to their low numbers but were summarized in combination with those examined in this study: Streptococcus pyogenes (944 strains), Streptococcus agalactiae (815 strains), Enterococcus faecium (146 strains), Branhamella catarrhalis (135 strains), Citrobacter diversus (128 strains), Klebsiella oxytoca (873 strains), Proteus vulgaris (438 strains), Serratia liquefaciens (266 strains), Pseudomonas cepacia (433 strains), Pseudomonas putida (154 strains), Xanthomonas maltophilia (272 strains), Vibrio parahaemolyticus (120 strains), Bacteroides fragilis (98 strains),

Bacteria↗
PubMed1987

Variations in genetic control of susceptibility to Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease. I. Differences between susceptible SJL/J and resistant BALB/c strains map near the T cell beta-chain constant gene on chromosome 6.

In some susceptible mouse strains, intracerebral (IC) inoculation of Theiler's murine encephalomyelitis virus (TMEV) results in a persistent infection leading to chronic demyelinating disease. Previous genetic analyses between susceptible SJL/J and resistant C57BL/6 mice indicated a role for multiple unlinked genes in the development of clinical and histopathological disease, including a major influence of the D region of the H-2 complex. In this study, genetic analysis of a different strain combination (susceptible SJL/J and resistant BALB/c) also demonstrates the involvement of multiple genes, but the H-2 genotype (H-2s and H-2d, respectively) does not appear to contribute significantly to susceptibility differences. In both segregation studies and recombinant-inbred (R-I) analysis, clinical and histopathological disease occurs in both H-2s homozygotes and H-2d homozygotes (as well as H-2s/H-2d heterozygotes), with the actual frequency related to the proportion of non-H-2 genome from the susceptible strain. There appear to be at least two non-H-2 genes involved in differential susceptibility of SJL/J and BALB/c to TMEV-induced disease. Analysis of R-I strains generated from BALB/c and SJL/J progenitors indicates linkage of at least one of these non-H-2 genes to those encoding the constant portion of the beta-chain of the T cell receptor on chromosome 6. Many genes may actually be involved, but each strain comparison defines a different subset of these loci--only those at which the two strains in question carry "functionally" different alleles. Thus, different strain comparisons may accent the roles of different genes in resistance to the same infectious organism or disease process. In addition to the genes identified thus far, there may be yet other genes contributing to development of TMEV-induced disease, but their recognition may require analysis of still other strain combinations.

Animals↗
PubMed1997

Murine susceptibility to radiation-induced pulmonary fibrosis is influenced by a genetic factor implicated in susceptibility to bleomycin-induced pulmonary fibrosis.

From evidence of interpatient variability in normal tissue sensitivity to radiotherapy and from radiation studies using inbred mouse strains, it is hypothesized that individual variation in susceptibility to radiation-induced pulmonary fibrosis is genetically controlled. A genetic model has been developed from the fibrosis-prone C57BL/6J and the fibrosis-resistant C3Hf/Kam mouse strains. Inheritance of the fibrotic phenotype was characterized in F1 and F2 (F1 intercross) generations derived from the parental strains. Genetic mapping was used to determine whether the quantitative trait loci (QTL), which influence susceptibility to bleomycin-induced lung fibrosis in these progenitor strains, could be implicated in susceptibility to radiation-induced lung fibrosis. Mice were treated with 14 or 16 Gy (60Co) to the whole thorax. The doses were selected to investigate the response at the LD50 and LD100 of C3Hf/Kam mice. The animals were sacrificed 33 weeks after treatment or when moribund. The percentage of lung with fibrosis for each mouse was quantified with image analysis of a histological section of the lung. For both the 14- and 16-Gy data sets, heritability was estimated at 38 +/- 11%, and the number of genetic factors influencing susceptibility to pulmonary fibrosis was estimated to be one or two. Two hundred fifty-five F2 intercross mice were genotyped with markers at the bleomycin loci on chromosomes 11 and 17 (chromosome 17 marker is at the major histocompatibility complex). Genetic linkage was established for the marker on chromosome 17 (P = 3.0 x 10(-6)), which accounts for 6.6% of the F2 phenotypic variance but not for the markers surrounding the QTL on chromosome 11 (P = 0.37). The inheritance data suggested that susceptibility to radiation-induced pulmonary fibrosis is a heritable trait controlled by two genetic loci, and through genomic mapping, a QTL on chromosome 17 was identified as one of the loci.

Animals↗
PubMed2006

Antimicrobial susceptibility pattern comparisons among intensive care unit and general ward Gram-negative isolates from the Meropenem Yearly Susceptibility Test Information Collection Program (USA).

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is a global, longitudinal antimicrobial resistance surveillance network of greater than 100 medical centers worldwide monitoring the susceptibility of bacterial pathogens to carbapenems and other broad-spectrum agents. Between 1999 and 2002, 15 US medical centers referred up to 200 nonduplicate isolates from clinical infections to a central processing laboratory. During this 4-year period, the antimicrobial activity of 11 broad-spectrum agents was assessed against 5389 bacterial isolates using Clinical and Laboratory Standards Institute (formerly National Committee for Clinical Laboratory Standards)-recommended methods with interpretive criteria. Analysis of the MIC results for pathogens isolated from patients hospitalized in intensive care units (ICUs) were compared to results from pathogens isolated in non-ICU settings. Among Enterobacteriaceae (3884 strains), the carbapenems (imipenem and meropenem) demonstrated the highest susceptibility rates (> or =98.7%) and with only a 1% increase in resistance for ICU isolates compared to non-ICU organisms. Other antimicrobial agents tested demonstrated consistently higher susceptibility rates against Enterobacteriaceae isolates from ICU (89.7-98.7%) and non-ICU (93.2-99.9%) areas. For the nonfermentative Gram-negative bacilli, the rank order of the most active agents having lowest percentage resistance rates were tobramycin (15.5%) < cefepime < imipenem < piperacillin/tazobactam < ceftazidime < meropenem (21.9%) for ICU isolates, and meropenem (7.8%) < cefepime < imipenem < piperacillin/tazobactam < ceftazidime < tobramycin (12.9%) among non-ICU strains. All tested agents showed lower susceptibility rates (range, 1.0-15.3%) and higher resistance rates (range, 0.1-15.1%) for both Enterobacteriaceae and nonfermentative Gram-negative bacilli among the ICU isolates compared to the non-ICU isolates (except for ciprofloxacin against Enterobacteriaceae). Continued surveillance of these broad-spectrum antimicrobial agents in both ICU and general hospital wards appears warranted to monitor the occurrence and spread of antimicrobial resistance in pathogens causing serious infections in these care areas and the possible emergence of resistance mechanisms that could compromise empiric carbapenem therapy.

Anti-Bacterial Agents↗
PubMed2001

Can antimicrobial susceptibility testing results for ciprofloxacin or levofloxacin predict susceptibility to a newer fluoroquinolone, gatifloxacin?: Report from The SENTRY Antimicrobial Surveillance Program (1997-99).

A serious problem confronting clinical laboratories and hospital formulary practices is the delayed availability of approved, commercially prepared susceptibility test reagents for newer antimicrobials. A current example is gatifloxacin, a new 8-methoxy fluoroquinolone with expanded potency against many Gram-positive pathogens. This study addresses the use of "surrogate marker" fluoroquinolones to predict susceptibility for gatifloxacin. Reference broth microdilution MIC results for 29,632 strains isolated in United States medical centers (SENTRY Antimicrobial Surveillance Program, 1997-99) were used: staphylococci (9,940 strains), enterococci (2,570), Streptococcus pneumoniae (3,784), Enterobacteriaceae (10,670) and Pseudomonas aeruginosa (2,668). Gatifloxacin interpretation categories were compared to those of ciprofloxacin and levofloxacin by regression statistics and error rate bounding analyses. For the Enterobacteriaceae, the absolute categorical agreement was 97.9 to 98.7% (false-susceptible or very-major error [VME], 0.03%-0.1%) for comparisons of both ciprofloxacin and levofloxacin with gatifloxacin. P. aeruginosa testing was more problematic (higher minor error rates), but acceptable at 0.6% to 1.1% VME and a 85.7% to 89.9% overall agreement. Ciprofloxacin results used to predict gatifloxacin in Gram-positive species was almost without VME (0.0%-0.2%) because gatifloxacin was significantly superior against these species, especially for S. pneumoniae, where gatifloxacin (MIC(90,) 0.5 microg/ml) was fourfold more potent than levofloxacin (MIC(90,) 2 microg/ml). The preferred gatifloxacin predictor drug was ciprofloxacin for all species except S. pneumoniae and P. aeruginosa, where levofloxacin results had a slightly greater predictive value. Susceptibility testing results for selected currently available fluoroquinolones can be used to predict susceptibility to gatifloxacin with high confidence. Many Gram-positive cocci, however, will be categorized as false-resistant by this interim method since gatifloxacin has a 11% to 34% wider spectrum of activity compared to ciprofloxacin when testing staphylococci and enterococci. Clinical laboratories can reliably use these suggested "surrogate markers" until reliable tests for gatifloxacin become available.

Anti-Infective Agents↗