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Frequent silencing of fragile histidine triad gene (FHIT) in Burkitt's lymphoma is associated with aberrant hypermethylation.

The fragile histidine triad (FHIT) gene, a potential tumor-suppressor gene, is frequently inactivated in multiple human cancers. However, the FHIT gene remains largely unexplored in Burkitt's lymphoma (BL). Hence, we assessed whether loss of FHIT expression occurs in BL, and, if so, what is the mechanism of such loss. Lack of protein expression was observed in 50% of BL cell lines. Methylation-specific polymerase chain reaction (MSP) showed that 45% of BL cell lines carried aberrantly methylated FHIT alleles. Sequencing of bisulfite-treated DNA confirmed these data and indicated a very high density of methylation in all methylated alleles. Real-time, quantitative reverse-transcription PCR analysis indicated that attenuation of full-length FHIT transcription was correlated with methylation. Sequencing of transcripts illustrated that aberrant transcription resulting in loss of FHIT exons occurred more commonly in BL containing unmethylated FHIT genes. However, such transcripts often coexisted with full-length FHIT transcripts. Not surprisingly, therefore, loss of FHIT protein in BL correlated with CpG island methylation, rather than with aberrant transcription. FHIT methylation also was detected in 31% (16 of 51) of the primary BLs examined, including 2 samples whose derived cell lines also manifested FHIT hypermethylation. Aberrant methylation can thus occur in vivo. In summary, this report provides evidence that epigenetic modification frequently results in loss of FHIT expression in BL.

Acid Anhydride Hydrolases↗

Expression of differentiation and adhesion molecules in sporadic Burkitt's lymphoma.

The phenotypic features of 44 cases of sporadic Burkitt's lymphoma (BL) were investigated by monoclonal antibodies (MoAbs). The majority of cases were positive for HLA-DR (97 per cent), CD19 (100 per cent), CD20 (92 per cent) and CD37 (83 per cent) pan-B markers, in accordance with the B-cell derivation of the tumour; the B-cell restricted markers CD21, CD22 and FMC7 reacted with 28 per cent, 66 per cent and 75 per cent of cases, respectively. Of the mantle zone B-cell specific MoAbs, CD1c was always negative, whereas CD23 and 2.7 were positive with one and two cases, respectively. CD39 was weakly reactive on two specimens, one of which was CD23+. The germinal centre specific MoAbs CD10 and CD77 (Burkitt's lymphoma antigen) displayed a heterogeneous pattern of reactivity and allowed to identify 4 subgroups: CD10+/CD77+ (44 per cent), CD10+/CD77- (15 per cent), CD10-/CD77+ (36 per cent) and CD10-/CD77- (5 per cent). Of 15 cases tested for the expression of CD11a and CD18 lymphocyte-function-associated (LFA-1) antigens and their ligand ICAM-1 (CD54), seven were positive and six negative for the three markers, while the other two cases expressed alternatively the two molecules. Analysis of the putative normal BL cell counterpart, identified with the CD77 marker in normal lymphoid tissues, showed that all CD77+ B-cells were constitutively CD11a+/CD18+, suggesting that BLs are likely to arise from a LFA-1 positive B-cell and may down-regulate these molecules during neoplastic transformation.

Adolescent↗

Accumulation of p53 protein correlates with tumour proliferative activity in EBV positive Burkitt's lymphoma.

p53 tumour suppressor gene is often found mutated in Burkitt's lymphoma (BL) cell lines and tumours. We analysed 35 BL tumours for the accumulation of p53 protein, and correlated the results with DNA flow cytometric data on the proliferative activity (SPF), and data on the presence or absence of Epstein-Barr virus (EBV) DNA. More than one-third (37 per cent) of the tumours showed accumulation of p53, which was considered to be consistent with mutation of the p53 gene. Tumours that were positive both for EBV DNA and p53 had significantly higher mean SPF than corresponding EBV DNA negative and/or p53 negative tumours. The proportions of tumour cells with accumulation of p53 appeared to correlate with tumour SPF only in EBV DNA positive BLs. However, there was no apparent association between accumulation of p53 and the presence or absence of EBV DNA. These findings are suggestive of multiple pathways in BL tumour progression.

Adolescent↗

IL6 and IL6 receptor expression in Burkitt's lymphoma and lymphoblastoid cell lines: promotion of IL6 receptor expression by EBV.

We have analysed a panel of different Burkitt's lymphoma (BL) and lymphoblastoid cell lines (LCLs) for the expression of IL6 and IL6 receptor (IL6R). Epstein-Barr-Virus (EBV) positive or negative BL cell lines and the corresponding lymphoblastoid cell lines (LCL), derived from EBV immortalized mononuclear cells of the BL patients, were tested for the expression of IL6 mRNA and protein by Northern blot experiments and ELISA, and for the expression of the IL6R mRNA and protein by Northern blot Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) and flow cytometry. Our results demonstrate that six out of 19 Burkitt's lymphoma cell lines produced IL6 constitutively. All three cell lines infected with the EBV substrain B95-8 (B95-8 convertants) produced IL6, in contrast to the original EBV negative lines and to the cell lines infected with the EBV substrain P3HR1 (P3HR1 convertants). The produced IL6 was biologically active as shown by proliferation of the IL6 dependent cell line TEPC 1033 C2. The two BL cell lines with the highest level of IL6 production (190 pg/ml and 550 pg/ml) expressed in addition IL6R molecules on the cell surface. Monoclonal antibodies directed against IL6 did not inhibit the growth of these two BL cell lines, thus excluding autocrine stimulation in these lines. IL6R expression could be further demonstrated in all LCLs analysed, in five out of seven EBV positive BLs and two out of three B95-8 convertants, but only in one out of the six EBV negative BL cell lines. Our results suggest that EBV in immortalized B cells and in Burkitt's lymphoma cells can promote IL6 receptor expression.

Base Sequence↗

Differential expression of HLA antigens on human B-cell lines of normal and malignant origin: a consequence of immune surveillance or a phenotypic vestige of the progenitor cells?

Pairs of BL-derived cell lines and in vitro EBV-transformed LCLs, derived from the same patient, were compared for the expression of MHC class-I antigenic determinants as shown both by monoclonal antibody (MAb) binding and by sensitivity to HLA-specific CTL clones. BL lines expressed all polymorphic determinants tested at a lower level than the corresponding LCLs, as indicated by the binding of the MAbs AUF 5.13 (anti-HLA A3,A11), GS 142.1 (anti-HLA A1), GS 114.1 (anti-HLA A24), GSP 35.1 (anti-HLA A2,A28), GSP 55.1 (anti-HLA A25,A32), TER MA32 (anti-HLA A32), GSP 145.2 (anti-HLA B27), B27 M.1 (anti-HLA B27,B7) and GSP 8.1 (anti-HLA B8). The difference was most pronounced for HLA A11 and least for B27,A1 and B8 with intermediate differences for the other specificities. The BL lines were also less sensitive to lysis by HLA-specific CTL clones directed to the same and to additional antigens. The polymorphic determinants detected by the AUF 5.13 and GSP 35.1. MAbs were expressed at a lower level in resting T and B cells compared to mitogen- and EBV-induced blasts. An analogous change in the expression of polymorphic determinants was observed in EBV-converted sublines of originally EBV-negative BLs that have become more "LCL-like" after conversion. The appearance of B-cell activation markers was paralleled by the up-regulation of both the serologically defined and the CTL-target epitopes. The findings suggest that the low expression of HLA determinants on the BL cells is a phenotypic vestige of the normal BL precursor.

Antibodies, Monoclonal↗

Tumorigenicity of EBV-carrying lymphoblastoid cell lines (LCLs): distinctive grading in SCID mice.

The in vitro and in vivo growth of lymphoblastoid cell lines (LCLs), Burkitt lymphomas (BLs) and PBL-derived immunoblastomas in SCID mice was studied in parallel. Most, but not all, of the LCLs tested were tumorigenic in SCID mice. Long-term culturing in vitro was not a necessary prerequisite for tumorigenicity. There was a good correlation between in vivo and in vitro growth. Three major classes of cells could be distinguished on the basis of their growth properties.

Animals↗

Expression of the Epstein-Barr virus (EBV)-encoded membrane protein LMP1 impairs the in vitro growth, clonability and tumorigenicity of an EBV-negative Burkitt lymphoma line.

In a previous study on several independently established Epstein-Barr virus (EBV)-converted sublines of the EBV-negative Burkitt lymphoma (BL) line BL41, we found that expression of the virally encoded membrane protein LMP1 was accompanied by reduced agarose clonability and tumorigenicity. In order to investigate whether LMP1 can induce these phenotypic changes by itself, we have now studied the growth in suspension culture, the clonability in agarose and the tumorigenicity in immunosuppressed and SCID mice of 4 LMP1-transfected sublines of BL41 that carry the gene under the control of the ZnSO4-inducible metallothionein promoter. Expression of LMP1 at levels comparable to those detected in EBV-transformed lymphoblastoid cell lines (LCL) correlated with impairment of growth in suspension and reduction of clonability and tumorigenicity. Only minor changes were observed in transfectants expressing low LMP1 levels. Up-regulation of LMP1 by ZnSO4 treatment of the low LMP1 clone MTLM5 was accompanied by a slowing down of proliferation, increased cell clumping and decreased clonability. The results suggest that expression of LMP1 at levels which are compatible with immortalization of normal B-cells antagonizes the ability of BL cells to grow in vitro and in vivo, and illustrate a possible mechanism by which down-regulation of this viral antigen may favor tumorigenicity in EBV-carrying BLs.

Animals↗

The Epstein-Barr virus latent membrane protein-1 (LMP1) induces interleukin-10 production in Burkitt lymphoma lines.

Human interleukin-10 (h-IL-10) is a pleiotropic cytokine with stimulatory activity on B-lymphocytes. Recent evidence indicates that infection with Epstein-Barr virus (EBV) induces h-IL-10 production in B-cells and that this cytokine may contribute to EBV-induced B-cell transformation. It is not known whether h-IL-10 induction by EBV correlates with distinct phenotypic features of the infected cells or with the expression of particular viral genes. We have approached these questions by investigating the expression of h-IL-10 mRNA in a panel of B-cell lines including: in vitro EBV-transformed lymphoblastoid cell lines (LCLs), EBV-carrying Burkitt lymphoma (BL) lines, EBV-negative BL lines and their sublines infected with different EBV strains, or transfected with the transformation-associated viral gene. h-IL-10 mRNA was detected by reverse-transcriptase-assisted (RT)-PCR in a subset of EBV-negative BLs and in all EBV-positive BL lines and LCLs investigated except Daudi. This cell line carries an EBV nuclear antigen (EBNA)-2 gene-defective virus strain. h-IL-10 mRNA was induced by conversion of 3 EBV-negative and h-IL-10-negative BL lines (BL41, BL47 and BL49) with the transforming, B95.8-derived EBV strain. P3HR-I virus convertants that do not express the viral EBNA-2 and the EBV latent membrane protein (LMP)-1, and fail to progress towards a LCL-like cell phenotype, showed no evidence of h-IL-10 up-regulation. Expression of LMP1 was sufficient to induce h-IL-10 mRNA in transfected sublines of the EBV-negative DG75 and BL41 cell lines, whereas expression of EBNA1, 2, 5, or 6 had no effect. h-IL-10 was detected in the culture supernatants of the LMP1 transfectants by specific ELISA assays. The present findings confirm the role of LMP1 in the transactivation of a wide variety of cellular genes which may be involved in EBV-induced B-cell transformation.

Antigens, Viral↗

Restricted expression of EBV latent genes and T-lymphocyte-detected membrane antigen in Burkitt's lymphoma cells.

Certain newly established Epstein-Barr virus-containing Burkitt's lymphoma cell lines do not express the cytotoxic T-lymphocyte-detected membrane antigen (LYDMA) through which EBV infection is normally controlled by the host. When the EB virus recovered from these BL lines was used to transform peripheral blood lymphocytes from seronegative donors, the lymphoblastoid cell lines (LCLs) that arose were all LYDMA positive. This indicates that the LYDMA-negative nature of the BLs is not the result of a mutation in the resident viral genome but is rather a specific adaptation in those cells, perhaps permitting evasion of the host immune surveillance in tumour development. A comparison of the EBV gene expression in six LYDMA-negative and two LYDMA-positive BL lines and in their corresponding LCLs revealed that several of the BL lines did not express all of the viral gene products classically associated with latent transformation by EBV. Four out of eight cell lines showed restricted expression of the latent membrane protein (LMP) and/or the EB nuclear antigen, EBNA 2. A new level of EBV gene regulation therefore appears to be operating in some of the BL cell lines. The patterns of expression of EBV genes in the cell lines did not show any correlation with the known susceptibility of the lines to T cell killing.

Antigens, Surface↗

Reduced signal transduction through glucocorticoid receptor in Burkitt's lymphoma cell lines.

Signal transduction through the glucocorticoid receptor (GR) was shown to be significantly reduced in Epstein-Barr virus (EBV)-positive group I Burkitt's lymphoma (BL) cell lines compared to human B-lymphocytes immortalized by EBV (LCLs). On the basis of hormone binding assays, nuclear DNA binding activity, and transactivation assays the response was reduced 5- to 10-fold. Direct sequence analysis of the expressed glucocorticoid receptor mRNA in two BL cell lines indicated that the phenotype did not result from mutation of the GR gene. By preparing a high-titer polyclonal antiserum against the t-1 region of the human GR, we further showed that the deficient GR response in BLs is largely reflected in reduced GR steady-state protein levels in BL cells compared to LCLs. However, the level of GR mRNA varies less between the BL cell lines and the LCLs. The Cp promoter of EBV which normally drives expression of the EBNA gene family in EBV-immortalized LCLs contains a functional glucocorticoid response element. Transfection of GR expression constructs to group I BL cells converted the GR response to approximately LCL levels both with respect to hormone binding and glucocorticoid-dependent transcription of a glucocorticoid-dependent promoter. A modest activation of EBNA-2 expression was seen in some such cell lines, suggesting that the lower GR response contributes to the down-regulation of EBNA expression observed in BL.

Antigens, Viral↗

Differential expression of viral and human interleukin-10 (IL-10) by primary B cell tumors and B cell lines.

Human and viral interleukin-10 (IL-10) possess growth factor activity for human B cells and may act as autocrine growth factors in B cell malignancies. To study this possibility we have measured viral (v) and human (h) IL-10 expression in EBV-positive and negative B lineage tumors and tumor cell lines. Previous studies demonstrated IL-10 expression in cell lines and now we describe the pattern of IL-10 expression in primary Burkitt's lymphoma (BL) tumor biopsies and in BL lines of defined phenotypes. vIL-10 was expressed during the lytic (productive) phase of EBV infection, but not during virus latency. Although hIL-10 was expressed in the majority of B cell lines, it was not expressed in two BL biopsy specimens. Expression of hIL-10 did not correlate with the presence of EBV, but was associated with the differentiation state of the B cell line. Thus, vIL-10 may enhance the persistence of B cells infected at sites of virus replication, and while hIL-10 may be a factor in the growth both in vivo and in vitro of some BLs and EBV-transformed B cells, it is not an absolute requirement.

B-Lymphocytes↗

[Results of a dietary survey in adults in Erfurt in 1991/92: nutritional intake].

A dietary survey using weighted 3-day-records was carried out in the sample of the third MONICA risk-factor survey in the Thuringian city of Erfurt (eastern Germany) in 1991/92. The aim was to collect detailed intake data in a defined population after the first phase of consolidation on the food market after the German reunification. The dietary sample consisted of 1,118 men and 1,179 women aged 20-64 years; we received 469 acceptable records from men and 333 from women. The German national nutrient datafile BLS (version 2.1) was used to code the records and for the transformation into nutrients. Mean energy intake in men was 2,624 kcal per day, 15.3% came from protein, 40.0% from fat, 38.5% from carbohydrates and 6.0% from alcohol. Corresponding figures for women were 1,916 kcal per day, 15.8%, 40.5%, 41.5% and 2.1%. Only a small percentage of participants achieved the recommendations of the German Society for Nutrition for the intake of selected nutrients.

Adult↗

The RAG cell line defines a new complementation group of MHC class II deficiency.

We previously described RAG, a mouse adenocarcinoma cell line, as deficient for the induction of major histocompatibility (MHC) class II antigens by IFN-gamma, but responding normally for MHC class I antigen stimulation and anti-viral protection. We had established that the fusion of RAG with various human cell lines restored the induction of MHC class II antigens, whenever the human chromosome 16 was present in somatic cell hybrids. Here we show that the RAG cell line does not exhibit any induction by IFN-gamma of DMA, DMB, and the invariant chain (Ii) mRNAs, and that the induction is restored in somatic cell hybrids containing human chromosome 16. In order to define the gene (designated F16) affected in the RAG cells, we performed a complementation analysis by fusing RAG with previously described human cell lines defective for MHC class II antigen expression (e.g., BLS cell lines), and which belong to five different complementation groups. Our data show that the resulting somatic cell hybrids present an inducible expression of mouse MHC class II antigens, Ii, DMA, and DMB. Therefore, the RAG cell line represents a yet undescribed cellular mutant affected in the expression of MHC class II antigens. In addition, we demonstrate that MHC class II antigens can be constitutively expressed in the RAG cell line when transfected with the cDNA encoding human CIITA driven by the RSV LTR promoter. Since the complementation analysis assessed that F16 and CIITA are distinct, our data suggest that F16 is required for the expression of CIITA.

Animals↗

The complexity of the Epstein-Barr virus infection in humans.

The Epstein-Barr virus (EBV) was isolated 40 years ago from cultures of Burkitt lymphoma cells (BL). The tumor was encountered in Africa and exhibited characteristical geographical, clinical and pathological features. Serological studies revealed that the virus is ubiquitous in humans. The primary infection is often accompanied by the syndrome of acute infectious mononucleosis (IM). It can induce malignant proliferation of B lymphocytes in conditions of immunodeficiency. EBV can immortalize B lymphocytes in culture. These cells carry the virus as episomes and express 9 virally encoded proteins. Their immunological recognition constitutes the surveillance which is responsible for the healthy virus carrier state. The main virus reservoir is represented by a low number of resting B lymphocyte which contain the viral genome but do not express its transformation proteins. The viral genome is detectable in all African BLs, in variable proportions of nasopharyngeal carcinoma, Hodgkin's disease, T cell lymphoma, lymphoepithelial like carcinoma, gastric carcinoma and leiomyosarcoma cases. The role of EBV in the genesis of these tumors is unknown.

Herpesviridae Infections↗

["Topless" cardiopulmonary resuscitation? Should heart-lung resuscitation be preformed without artificial resuscitation?].

A paper published in various US journals on Emergency Medicine in 1997, has raised considerable concerns. The authors question if it is justified to continue to recommend initial ventilation as part of basic CPR when performed by lay-bystanders. A few aspects need to be discussed and some questions have to be answered before any changes in the current recommendations may even be considered: e.g. 1. How convincing does the available evidence support the following hypotheses: 1.1. Lay CPR without mouth-to-mouth-ventilation provides better outcome after cardiac arrest than lay CPR with mouth-to-mouth-ventilation. 1.2. Endotracheal intubation may be detrimental in patients suffering from hemodynamic compromises, particularly from VF. 2. Is it scientifically and ethically acceptable to design and perform prospective randomized controlled trials (RCTs) to evaluate the efficacy of those components of BCLS and ACLS which have in accordance with AHA-, ERC Guidelines and ILCOR Statements in the past been applied in millions of cardiac arrest victims and have obviously enabled the patients to lead a meaningful life after survival; under conditions of the proposed study design patients of the study group would be left without the treatment option ventilation, thus diminishing their chances of survival. Ad 1: The arguments presented by the authors are hardly convincing. The authors themselves state elsewhere that reluctance to perform mouth-to-mouth-ventilation should not represent a major problem because most cardiac arrests of cardiac etiology occur at home and in the presence of a relative or friend. Moreover, unreliable recommendations for mouth-to-mouth-ventilation (AHA), lack of training, retention of skills and knowledge, and a deficit in motivation include the main causes of the disappointingly low figures of bystander CPR worldwide. This situation cannot be improved simply by eliminating a lifesaving component of CPR-ventilation. Instead, the proposal to abandon the administration of unreasonably high ventilation volumes (800-1200 ml/breath) from the present guidelines and to recommend volumes ranging from 400-500 ml/breath recently made by the ERC should be given serious consideration. Furthermore, equipment and training manikins need to be adapted to these more reasonable volumes. Independently of the mechanisms of slow decreases in SaO2 after cardiac arrest (provided no compressions are performed) independently of gasping, ventilatory effects of standard compression or ACD-HCPR in the absence of mouth-to-mouth-ventilation, it is essential to realise that the patient's airways need to be maintained open at all times (this is unlike animal experiments where the airways are primarily kept open by the respective tissue structures): The minimum requirement of First Responder CPR is the guarantee that open airways are maintained. It may possibly be discussed if the present sequence of ABC might be changed to CAB, a practice adopted in the Netherlands many years ago, however, outcome trials an CAB have not been published to date. In addition, greater demands should be made of training requirements in BLS, attendance of refresher courses should be required, and other groups of the population should be included into these programmes than only relatives or friends of patients at risk of a cardiac arrest. The programmes need to be made mandatory for greater variety of groups and individuals to increase the efficacy and efficiency of bystander resuscitation. The hypotheses made by the above-mentioned authors are neither scientifically nor ethically acceptable. Ad 2: Pepe's argument regarding the efficacy of endotracheal intubation (ETI) in VF-patients has not been scientifically proven and lacks conclusive evidence. ETI serves to protect the airways and lungs against aspiration of regurgitated material and to facilitate artificial ventilation including PEEP, both under anaesthesia and resuscitation. The efficacy of ETI in the OR has long b

Cardiopulmonary Resuscitation↗

Dietary intake and smoking--results from a dietary survey in Erfurt in 1991/92.

Data relating to 422 men and 315 women aged 20 to 64 years were collected in 1991/92 using 3-day weighed records. The national German food composition file BLS 2.1 was used for food coding and calculation of nutrients. Age adjusted mean daily intakes were presented. Food intake habits of smokers and non-smokers showed distinct differences: for instance, non-smokers of both genders are more fresh fruit (m: 166 g vs. 119 g, p = 0.0001; f: 180 g vs. 147 g, p = 0.0009), more milk and milk products (m: 195 g vs. 121 g, p = 0.0108; f: 176 g vs. 136 g, p = 0.0004), and drank less coffee (m: 401 g vs. 457 g, p = 0.0103; f: 387 g vs. 491 g, p = 0.0003). As a result, intakes of various nutrients also differed. For example, smokers had lower intakes of fibre, selected vitamins, and minerals. The tendency toward an unhealthier dietary pattern in smokers was in accordance with findings from various industrialized Western countries.

Adult↗

Supplements as a source of micronutrient intake in middle-aged men in southern Germany: results of the MONICA dietary survey 1994/95.

Survey data on contemporary supplement intake in Germany are scarce, and the contribution of supplements to nutrient intake is especially unclear. In the MONICA Project Augsburg a dietary survey using 7-day weighed records was carried out in a subsample of 607 eligible men aged 45-64 years from the city of Augsburg (participation 430 men = 71%) in 1994/95. Participants also reported their intake of supplements. The German national food data base BLS (version 2.1), which was used to code the records and calculate the nutrients, had to be complemented by nutrient data of supplements and fortified foods. On a group level the maximum mean percentage contribution of supplements to the intake of a micro nutrient was 4.0% (vitamin C). On an individual level, however, up to 4.0% of the men were found to receive more than 50% of their intake of selected micronutrients from supplements. It is, therefore, recommended to ask for supplement intake in future dietary surveys within Germany.

Databases, Factual↗

Survey of the susceptibility of urinary isolates to antibacterial agents in 2003.

In 2003, 826 uropathogenic strains were obtained from the urine of our patients. We assessed their activities to antibacterial agents based on the minimal inhibitory concentration (MIC) breakpoints recommended by the National Committee for Clinical Standards (NCCLS). Methicillin-resistant strains accounted for about 70% of Staphylococcus aureus and Staphylococcus epidermidis. The most common gram-positive species was Enterococcus faecalis (15.6%). Enterococcus faecium was the most resistant of the enterococcal species, and the rate of susceptibility to beta-lactams (BLs), fluoroquinolones (FQs), and tetracyclines (TCs) was 0%, 6%, and less than 18%, respectively. Escherichia coli accounted for over 50% of the gram-negative bacilli. The proportion of FQ-resistant or intermediate strains was over 20%, and four of these strains (1.1%) were suspected of producing extended-spectrum beta-lactamase (ESBL). All the ESBL-producing strains (ESBLs) possess resistance to FQs. Over 95% of Klebsiella pneumoniae was susceptible to all agents. The distribution of antimicrobial activity against Pseudomonas aeruginosa indicated a decrease in the number of multidrug-resistant strains and an increase in strains susceptible to all agents. Some differences existed in the resistance to antibacterial agents among Proteus species. No ESBL-producing or multidrug-resistant strain was isolated from Serratia marcescens. This survey suggests that serious clinical problems will result from the increasing number of enterococcal species with multidrug resistance in gram-positive cocci, and isolates of ESBL-producing or FQs-resistant strains in gram-negative bacilli.

Anti-Bacterial Agents↗