Similar Resistance Patterns Research Articles

Demonstration of persistence of Salmonella typhimurium in an AIDS patient by molecular methods

We document microbiological persistence of the same Salmonella typhimurium strain in an AIDS patient during 7 months of clinical observation despite prolonged quinolone therapy. Persistence was demonstrated by phage types that closely resembled one another, similar antibiotic resistance patterns, conserved restriction fragment length polymorphism of chromosomal DNA digested with different DNA restriction enzymes, identical ribotypes, and IS200 types in four characterized sequential isolates of S. typhimurium.

Construction and characterization of isogenic O‐antigen variants of Salmonella typhi

A 7.5 kb KpnI-generated fragment, from within the rfb cluster of Salmonella typhimurium LT2 that encodes abequose synthase (the rfbJ gene) which is necessary for O4 antigen synthesis, and flanking sequences, was inserted into a suicide vector. Using allelic exchange techniques, these rfb sequences of S. typhimurium were integrated into the rfb clusters of wild-type Salmonella typhi Vi-positive strain ISP 1820 (i.e. serotype O9,12; Vi+; H-d), S. typhi Vinegative strain H400 (i.e. serotype O9,12; Vi-; H-d), and a double aro mutant of S. typhi ISP 1820, strain CVD 906, resulting in the isolation of strains H325, H404 and CVD 906-O4, respectively. Immunoblot analysis of lipopolysaccharide (LPS) purified from H325, H404 and CVD 906-O4 demonstrated that these strains express the O4 antigen (an abequose residue) in place of the O9 antigen (a tyvelose residue) in the LPS molecule. Hence, the serotype of H325 is O4,12; Vi+; H-d and the serotype of H404 is O4,12; Vi-; H-d. DNA hybridization analysis of chromosomal DNA from H325, H404 and CVD 906-O4 confirmed that a precise recombination event within sequences flanking rfbSE of S. typhi (which encodes the enzymes necessary for cytidine diphosphate-tyvelose synthesis) resulted in replacement of rfbSE with rfbJ (which encodes abequose synthase and is necessary for O4 synthesis) of S. typhimurium in strains H325, H404 and CVD 906-O4. The resistance of each strain to the bactericidal effects of guinea-pig serum (GPC) was assessed. Whereas ISP 1820, H325 and H404 exhibit similar resistance patterns in GPC, strain H400 is sensitive to the bactericidal effects of GPC.(ABSTRACT TRUNCATED AT 250 WORDS)

Apramycin-resistant Escherichia coli isolated from pigs and a stockman.

Escherichia coli serotype O147:K89:K88a,c was found to be associated with outbreaks of diarrhoea in preweaner pigs of up to 4 weeks of age on a pig unit. Resistance to apramycin, gentamicin, netilmicin, tobramycin and other antibiotics was associated with conjugative plasmids of approximately 62 kb. The presence of a gene which encoded for the aminoglycoside acetyltransferase enzyme AAC(3)IV was confirmed by DNA hybridization. Samples collected during the following 12 months revealed widespread dissemination of these resistance plasmids in non-serotypable, non-haemolytic E. coli throughout the farm. Apramycin-resistant E. coli were also isolated from a stockman and it appeared from plasmid profile analysis and antibiotic sensitivity testing that the human isolates carried the same plasmid as that carried by the porcine E. coli. Klebsiella pneumoniae, with a slightly smaller conjugative plasmid and similar resistance pattern, was isolated from the stockman's wife.

Comparison of the effectiveness of different methods of screening for bacterial soft rot resistance of potato tubers

Tubers from eight potato cultivars (cvs) grown at two different locations in Wisconsin were tested for bacterial soft rot resistance using different inoculation techniques. The procedures included 1) point inoculations of tubers with different inoculum levels followed by incubation in ambient or low oxygen condtions, 2) inoculation of mechanically bruised tubers followed by incubation in a mist chamber, and 3) a standard slice inoculation method. The point titration test followed by incubation in dew chamber and the mist chamber-bruise test showed similar patterns of resistance for cultivars that were used in these experiments. These two methods are considered to be effective for screening potato tubers for bacterial soft rot resistance. Point titration methods are very useful if only limited numbers of tubers are available. The mist chamber-bruise test is simpler than the other procedures; however, to obtain reproducible results large numbers of tubers are required. Because of the great variability of the results obtained in inoculation of slices, the reliability of this approach can be questioned as a standardized method for evaluation of resistance. Tubers of somatic hybrids ofS. brevidens andS. tuberosum and their sexual progeny were significantly more resistant to bacterial soft rot than tubers of moderately resistant cultivars when evaluated by each of the assay procedures.

Potato resistance to soft-rot erwinias is related to cell wall pectin esterification

Resistance to soft-rot erwinias of two siblings (4708 and 4680) from a backcross between a Solanum brevidens × S. tuberosum subsp. tuberosum somatic hybrid and cv. Katahdin and of three commercial potato cultivars (Record, Estima and Katahdin) was examined. Tuber cortex was generally more resistant than the medulla when inoculated with 103 cells ml-1 of Erwinia carotovora subsp. atroseptica (strain SCRI 1039). The extent of rotting in all genotypes was similar for each of the two tissues whether under aerobic or anaerobic conditions. The only exception was 4680 in which lesions were considerably smaller. A similar resistance pattern was obtained with stem tissue of the different potatoes, and with E. carotovora subsp. carotovora and E. chrysanthemi. The percentage esterification of pectin in cell wall extracts was generally greater in the tuber cortex than in the medullary tissue and was 2·4 and 1·6 times greater in the medulla (69·4%) and cortex (94·1%) of 4680 respectively than in corresponding tissues of the other genotypes which were all similar. Pectin esterification in stem cell walls was twice as great in 4680 (69·3%) than in the other potatoes. Levels of Ca2+ in tubers were greater in the cortex than in the medulla but were not different between genotypes, including 4680. Pectate lyase (PL) activity of SCRI 1039 was low with cell wall extracts of 4708 and 4680 as substrate but increased in the presence of pectin methyl esterase (PME), especially with higher concentrations of substrate from 4680. Discs of tuber cortex were also more resistant to maceration by PL than discs from the medulla, while medullary and cortical tissues of 4680 were respectively 2·1 and 1·7 times more resistant to maceration than the corresponding tissues of the other genotypes. Maceration was generally more rapid if PME was also present. The results suggest that there is an association between tuber resistance to erwinias and pectin esterification which, as a preformed resistance characteristic, would be operative under anaerobic conditions in which disease usually develops.

Identification of a novel mutation in the gene encoding the β‐triiodothyronine receptor in a patient with apparent selective pituitary resistance to thyroid hormone

We investigated whether the first patient (L-F3) reported as having selective pituitary resistance had a mutation in the hTR beta gene. We compared the clinical parameters of this case with those of patients with generalized resistance to thyroid hormone. The patient, L-F3, was part of a study at the NIH to identify mutations by sequencing the hTR beta gene in kindreds with thyroid hormone resistance. The clinical data of L-F3 as well as patients with generalized resistance to thyroid hormone were compared and analysed retrospectively. We amplified by the polymerase chain reaction and then sequenced exons 5 to 10 of the hTR beta gene in L-F3 and a normal control. Upon finding the mutation in L-F3, we measured the affinity constant of this mutated hTR beta receptor. Criteria developed previously were used to assess tissue responsiveness to thyroid hormone of L-F3. We identified a C to T transition at base 1297 in codon 333 of the hTR beta gene in the first patient (L-F3) reported as having apparent selective pituitary resistance. This base substitution resulted in more than a four-fold decrease in T3-binding affinity for the hTR beta 1 receptor. The mutation of L-F3 occurred in the dimerization domain of exon 9, a region where the majority of mutations of kindreds with generalized thyroid hormone resistance have been found. Furthermore, the nucleotide substitution at base 1297 found in the apparent selective pituitary resistant case, L-F3, was the same as in an unrelated patient (K-T3) with generalized resistance to thyroid hormone. As a result, we compared the clinical parameters of both patients and found that they had similar patterns of resistance in several tissues. Besides the bone resistance present in both kindreds, the apparent selective pituitary resistance case also had liver and neuromuscular resistance. These findings suggest that apparent selective pituitary resistance and generalized resistance to thyroid hormone are not qualitatively different syndromes. Nevertheless, identification of selective pituitary resistance is a useful clinical distinction since such patients with clinical and biochemical features of hyperthyroidism appear to benefit from reduction in serum thyroid hormone concentrations. In contrast, patients with more conventional forms of thyroid hormone resistance require no treatment or may benefit from increased concentrations of thyroid hormone.

長野県山口村の阿寺断層の土壌ガス中のラドン濃度とγ線スペクトロメトリーの違いについて

Dipole-dipole electric surveys, radon measurements in soil-gas and γ-ray spectrometry were carried out over the Atera active fault in Yamaguti village, Nagano Prefecture. The method for measuring radon in soil-gas are granular activated carbon in thin cylindrical canister.The results of radon measurements are correlated with the underground structure by electric survey and the γ-ray spectrometry. The underground structures in a pseudo-profiles of specific resistance contour show faults as a trace connected margin to margin of high specific resistance zones. From similar specific resistance patterns, we could find out several faults.Several peaks over Atera faults appeared in the profile of radon concentration along survey line A. The highest radon concentration peak corresponds to the one of faults estimated from electrical prospecting.Comparing the radon concentration to equivalent γ-ray spectrometry shows a poor correlation between radon concentration and γ-ray activities of 214Bi.The poor correlation seems to be due to that γ-ray activities 214Bi is reflecting uranium content of soil particles and radon concentration is radon content of soil-gas in pore space of soil.

Selection of tumor cell variants for resistance to tumor necrosis factor also induces a form of pleiotropic drug resistance.

This study has addressed the question of whether there may be some common mechanism underlying the induction or expression of acquired cytokine and drug resistance in a tumor cell line. This study employed the tumor-necrosis-factor(TNF)-sensitive U937 tumor cell line as a model system to determine if selection of a tumor cell variant for cytokine resistance would also result in drug resistance and vice versa. Variants were selected by culturing in the presence of purified recombinant TNF or a mixed-lymphokine-containing supernatant derived from concanavalin-A-stimulated peripheral blood lymphocytes. The resulting variants were resistant not only to TNF, but also to certain chemotherapeutic drugs. The variants were most resistant to colchicine and the Vinca alkaloids, requiring drug concentrations 50- to 5000-fold higher to mediate levels of cytotoxicity comparable to that seen with the parental U937. The variants were moderately resistant to cycloheximide, actinomycin D, and mitomycin C. In contrast, these lines were relatively sensitive to doxorubicin or daunomycin. This phenomenon was not unique to U937 cells since we obtained a similar pattern of drug resistance by selecting TNF-resistant variants of the WEHI-164 tumor cell line. The cytokine-selected U937 variants were still lysed by NK cells, although they were somewhat less sensitive than the parental U937. Both variants were relatively resistant to lysis by activated macrophages, probably because of their TNF resistance. In an alternative selection procedure, U937 variants were derived by culturing in the presence of increasing concentrations of colchicine. The resulting variants were relatively resistant to TNF, providing further support for the existence of some common mechanism operating in induction or expression of acquired cytokine and drug resistance. The resistance mechanism apparently does not involve the P glycoprotein since the cytokine-selected U937 variants do not overexpress the mdr gene. This study has demonstrated that selection of TNF-resistant variants results in coexpression of a unique form of drug resistance that is characterized by resistance to microtubule-active drugs but not to the anthracycline antibiotics and is not associated with overexpression of the mdr gene.

Antimicrobial resistance in Streptococcus pneumoniae: an overview.

Clinical resistance to penicillin in Streptococcus pneumoniae was first reported by researchers in Boston in 1965; subsequently, this phenomenon was reported from Australia (1967) and South Africa (1977). Since these early reports, penicillin resistance has been encountered with increasing frequency in strains of S. pneumoniae from around the world. In South Africa strains resistant to penicillin and chloramphenicol as well as multiresistant strains have been isolated. Similar patterns of resistance have been reported from Spain. Preliminary evidence points to a high prevalence of resistant pneumococci in Hungary, other countries of Eastern Europe, and some countries in other areas of Europe, notably France. In the United States most reports of resistant pneumococci come from Alaska and the South, but resistance is increasing in other states and in Canada. Pneumococcal resistance has also been described in Zambia, Japan, Malaysia, Pakistan, Bangladesh, Chile, and Brazil; information from other African, Asian, and South American countries is not available. The rising prevalence of penicillin-resistant pneumococci worldwide mandates selective susceptibility testing and epidemiological investigations during outbreaks.

Emergence of multidrug-resistant Plasmodium falciparum in Thailand: in vitro tracking.

Mefloquine was introduced into Thailand in 1985 for the treatment of Plasmodium falciparum infection. Recently, clinical failure of mefloquine was observed in southeastern Thailand, where an epidemic of falciparum malaria occurred. Beginning in 1984 and continuing until 1989, in vitro monitoring of P. falciparum isolates from Borai, a border district in the southeastern part of the country, showed a progressive decrease in mefloquine sensitivity until 1989; in 1990, the degree and prevalence of resistance accelerated. A similar pattern of resistance was observed for halofantrine, an antimalarial drug not yet commercially available in Thailand. In vitro sensitivity patterns of mefloquine and halofantrine elsewhere in the country remained relatively unchanged. These observations suggest a serious deterioration in available drugs for the treatment of falciparum malaria in southeastern Thailand that is predicted to spread throughout the country and Southeast Asia.

FLUDARABINE PHOSPHATE SELECTIVELY INHIBITS GROWTH AND MODIFIES THE ANTIGENIC PHENOTYPE OF HUMAN GLIOBLASTOMA-MULTIFORME CELLS EXPRESSING A MULTIDRUG RESISTANCE PHENOTYPE

Fludarabine phosphate (FLU), the 2-fluro derivative of Ara-A, 9-beta-D-arabino-furanosyl-2-fluoroadenine, has been shown to display both in vitro and in vivo antiproliferative activity toward a variety of murine tumors and human lymphoid malignancies. In the present study, we have determined the effect of FLU, alone and in combination with recombinant human fibroblast interferon (IFN-B), on in vitro growth, gene expression and the antigenic phenotype of human glioblastoma multiforme (GBM) cells displaying a multidrug sensitive and a multidrug resistant (MDR) phenotype. FLU exhibited a marked differential toxicity toward GBM-MDR cells versus the multidrug sensitive GBM parental cell line. Growth of GBM-MDR cells for seven days in 2.5 to 7.5 muM FLU resulted in a dose-dependent reduction or elimination of growth which persisted after removal of this agent. In contrast, recovery from FLU-induced growth suppression was observed in parental multidrug sensitive GBM cells. Acquisition of increased FLU sensitivity in GBM-MDR cells did not appear to result from selection for a subset of sensitive cells or an artifact associated with the DNA-transfection process. This conclusion is supported by the similar pattern of FLU resistance in GBM-18 clones isolated after transfection with a cloned hygromycin resistance gene and selection for resistance to hygromycin. The antiproliferative and toxic effect of FLU was increased in GBM-MDR cells by simultaneous growth in IFN-B and the toxic effect of FLU could be blocked in a dose-dependent manner by the simultaneous addition of deoxycytidine. In contrast, the toxicity of FLU toward GBM-MDR cells was not altered when cells were grown in the presence or absence of colchicine or by the administration of verapamil, which can reverse the MDR phenotype in GBM-MDR cells. The selective toxicity of FLU toward GBM-MDR versus GBM-18 cells was not associated with a consistent differential change in all of the GBM-18 MDR clones in the steady-state mRNA levels of a number of genes, including mdr-1, c-myc, c-fos, JunB, C-jun, proliferative cell nuclear antigen (PCNA), interferon stimulated gene-15 (ISG-15), fibronectin, tenascin, Class I HLA antigen, intercellular adhesion molecule I (ICAM-1), beta-actin or GAPDH. A common change observed in both parental GBM-18 cells and MDR GBM-18 clones exposed to FLU was an increase in the steady-state mRNA levels of deoxycytidine kinase (DCT). Analysis of the antigenic phenotype in GBM and GBM-MDR cells by fluorescence activated cell sorter (FACS) analysis using specific monoclonal antibodies (MoAbs) recognizing ICAM-1, Class I HLA antigen and a high molecular weight-melanoma associated antigen (HMW-MAA) indicated that FLU was generally more active as an immunomodulating agent in MDR versus non-MDR GBM cells. Although the mechanism underlying the differential effect of FLU toward GBM-MDR versus GBM cells is not presently known, the present findings indicate that the growth inhibitory and immunomodulatory effects of FLU are enhanced in cells expressing an MDR phenotype resulting from overexpression of a cell membrane localized 170,000 M(r) glycoprotein (P-glycoprotein).

Nationwide spread of Klebsiella oxytoca K55 in Swedish neonatal special care wards

In a nationwide survey of invasive bacterial infections in Swedish neonates, 36% of Klebsiella spp. were Klebsiella oxytoca serotype K55. This unexpectedly high proportion of K55 infections was due to clusters of infection in neonatal special care wards, and at first seemed attributable to nosocomial spread of a K. oxytoca strain of high virulence. Factors predisposing infants to infection were, however, found irrespective of whether the infecting strain was of serotype K55 or not. Additionally, the prevalence rates of a potential virulence factor, siderophore production, were similar among the two groups of strains. During the same period of time a K. oxytoca K55 with similar biochemical phenotype and drug resistance pattern was found to be spread among the neonates in 12 of 22 neonatal wards in Sweden. The increased proportion of invasive neonatal K. oxytoca K55 infections thus seemed to reflect a high rate of colonization rather than an increased virulence of the K55 strain.

Density of Imported Cabbageworms (Lepidoptera: Pieridae), Cabbage Aphids (Homoptera: Aphididae), and Flea Beetles (Coleoptera: Chrysomelidae) on Glossy and Trichome-Bearing Lines of Brassica oleracea

Two new glossy lines, the broccoli ‘Broc 5’ and the cauliflower ‘Glossy Andes’ with new genes for glossiness, had similar patterns of insect resistance to those of most other, previously tested glossy lines. Imported cabbageworm larvae, Pieris rapae (L.), were 80% fewer in natural infestations on glossy lines than on normal-wax standard varieties of the same crop, and cabbage aphids, Brevicoryne brassicae (L.), were reduced by over 95%. Unfortunately, all glossy lines tested were highly susceptible to the flea beetles Phyllotreta cruciferae (Goeze) and P. striolata (F.). A trichome-bearing broccoli line developed from an interspecies cross with Brassica incana Tenore was no better than the glossy lines because it had similar levels of flea beetle susceptibility, only a 55% reduction in imported cabbageworm larvae, and a 76% reduction in cabbage aphids, even in a line selected for relatively high trichome density. Artificial infestation of glossy and nornlal-wax lines with imported cabbageworm eggs showed that resistance in glossy lines acted on both the egg and larval stages; thus, even when ovipositional nonpreference was eliminated as a factor, there were 50-85% fewer imported cabbageworm larvae on glossy lines than on normal-wax standard lines.

Variation in resistance to herpes simplex virus type 1 of oligodendrocytes derived from inbred strains of mice.

Primary oligodendrocyte (OL) cultures from three inbred strains of mice with known differences in resistance to herpes simplex virus type 1 (HSV-1) infection in vivo (A/J, susceptible; BALB/cByJ, moderately resistant; C57BL/6J, resistant), also display a similar pattern of resistance in vitro. The nature of the in vitro resistance at the cellular level was investigated. Virus production at different m.o.i.s indicated that the differences in HSV-1 replication are m.o.i.-dependent. Overall, virus yield from the OL cultures infected at a multiplicity of 1 increased 48 h post-infection (p.i.); no additional enhancement occurred 72 h p.i. However, the difference in the replication capacity of the three OL cultures observed at 24 h p.i. persisted at 48 and 72 h p.i. Serial electron microscopy studies on infected OL cultures derived from the different murine strains suggested that the resistance to HSV-1 infection occurs at different stages during the replicative cycle. Virus was detected at the nuclear membrane 5 min p.i. in A/J cells, but was not observed until 120 min p.i. in BALB/cByJ cells, whereas virus could not be detected at the nuclear membrane of C57BL/6J cells, even at 24 h p.i. Virus adsorption, determined by assay of residual non-adsorbed virus infectivity and cell-associated, radiolabelled HSV-1, did not differ in the OL cultures. The cumulative data suggest that A/J cells display the same replication pattern as permissive CV-1 cells, whereas the major replicative blocks in the other two murine strains occur at the level of the cytoplasmic membrane in C57BL/6J OLs, and at the level of the nuclear membrane in BALB/cByJ cells.

Cross-Resistance to Herbicides in Annual Ryegrass (Lolium rigidum)

Lolium rigidum Gaud. biotype SLR31 is resistant to the herbicide diclofop-methyl and cross-resistant to several sulfonylurea herbicides. Wheat and the cross-resistant ryegrass exhibit similar patterns of resistance to sulfonylurea herbicides, suggesting that the mechanism of resistance may be similar. Cross-resistant ryegrass is also resistant to the wheat-selective imidazolinone herbicide imazamethabenz. The cross-resistant biotype SLR31 metabolized [phenyl-U-(14)C]chlorsulfuron at a faster rate than a biotype which is susceptible to both diclofop-methyl and chlorsulfuron. A third biotype which is resistant to diclofop-methyl but not to chlorsulfuron metabolized chlorsulfuron at the same rate as the susceptible biotype. The increased metabolism of chlorsulfuron observed in the cross-resistant biotype is, therefore, correlated with the patterns of resistance observed in these L. rigidum biotypes. During high performance liquid chromatography analysis the major metabolite of chlorsulfuron in both susceptible and cross-resistant ryegrass coeluted with the major metabolite produced in wheat. The major product is clearly different from the major product in the tolerant dicot species, flax (Linium usitatissimum). The elution pattern of metabolites of chlorsulfuron was the same for both the susceptible and cross-resistant ryegrass but the cross-resistant ryegrass metabolized chlorsulfuron more rapidly. The investigation of the dose response to sulfonylurea herbicides at the whole plant level and the study of the metabolism of chlorsulfuron provide two independent sets of data which both suggest that the resistance to chlorsulfuron in cross-resistant ryegrass biotype SLR31 involves a wheat-like detoxification system.

Two novel transferable extended-spectrum β-lactamases from Klebsiella pneumoniae in Tunisia

Two novel β-lactamases conferring multiresistance to antibiotics including oxyimino β-lactams have been identified in two nosocomial K. pneumoniae strains isolated in Tunis in 1986 and 1988. Both enzymes were encoded by ca. 150-kilobase plasmids. Donor and transconjugant strains producing these enzymes exhibited highly similar pattern of resistance (CTX phenotype) to β-lactams including penicillins and oxyimino β-lactams e.g. cefotaxime, ceftriaxone, ceftazidime, and aztreonam. High and variable synergy (16 to 1066-fold) was obtained when combined to 0.1 μg/ml of clavulance (β-lactamase inhibitor). The isoelectric points of these two enzymes were 5.4 and 6.4. These β-lactamases differed from TEM types by hydrolysis for cefotaxime or ceftriaxone but were inhibited by clavulanate and cloxacillin. DNA hybridization studies suggested that the genes of these enzymes may be derived from genes encoding TEM-type enzymes.

Two novel transferable extended-spectrum β-lactamases from Klebsiella pneumoniae in Tunisia

Two novel beta-lactamases conferring multiresistance to antibiotics including oxyimino beta-lactams have been identified in two nosocomial K. pneumoniae strains isolated in Tunis in 1986 and 1988. Both enzymes were encoded by ca. 150-kilobase plasmids. Donor and transconjugant strains producing these enzymes exhibited highly similar pattern of resistance (CTX phenotype) to beta-lactams including penicillins and oxyimino beta-lactams e.g. cefotaxime, ceftriaxone, ceftazidime, and aztreonam. High and variable synergy (16 to 1066-fold) was obtained when combined to 0.1 microgram/ml of clavulanate (beta-lactamase inhibitor). The isoelectric points of these two enzymes were 5.4 and 6.4. These beta-lactamases differed from TEM types by hydrolysis for cefotaxime or ceftriaxone but were inhibited by clavulanate and cloxacillin. DNA hybridization studies suggested that that the genes of these enzymes may be derived from genes encoding TEM-type enzymes.

Cassava-fermenting organisms

Organisms isolated during the fermentation of cassava tubers, as practised for ‘fufu’ production, includedBacillus subtilis, Pseudomonas alcaligenes, Lactobacillus plantarum, Corynebacterium manihot, Leuconostoc mesenteroides andPseudomonas aeruginosa. All isolates displayed amylase activity. Optimum growth and amylase activities of isolated organisms was at 42°C and between pH values 5 and 6. Isolated organisms also displayed similar patterns of antibiotic resistance. Plasmids purified from isolates could not be transferred or maintained inEscherichia coli RR1 cells.

The antimicrobial susceptibility of Pseudomonas pseudomallei. Emergence of resistance in vitro and during treatment.

We have measured the in-vitro activity of 27 antimicrobials against 211 clinical and ten reference strains of Pseudomonas pseudomallei. Imipenem was the most active antibiotic tested, followed by piperacillin, doxycycline, amoxycillin/clavulanic acid, cefixime, cefetamet, azlocillin and ceftazidime, all of which had MICs of less than or equal to 2 mg/l for the majority of strains. The measured MICs were dependent on the media and inocula used, to an extent which varied with the antibiotic class under test; MICs of ureidopenicillins were particularly inoculum-dependent. The beta-lactams and ciprofloxacin were bactericidal, whereas the agents conventionally used to treat melioidosis (doxycycline, chloramphenicol, sulphamethoxazole and trimethoprim) had bacteriostatic activity only. Strains highly resistant to chloramphenicol (MIC greater than or equal to 256 mg/l) emerged during treatment in 7.1% of patients. These strains were fully virulent, and frequently showed cross-resistance to tetracyclines, sulphamethoxazole, trimethoprim and ciprofloxacin, with paradoxical increased susceptibility to beta-lactams and aminoglycosides. Similar resistance patterns were seen in mutants generated in vitro and two reference strains. One strain with isolated ceftazidime resistance, reversible by clavulanic acid, emerged during treatment. Several of the new beta-lactam antibiotics are of potential value in the therapy of P. pseudomallei infections. Patients should be carefully monitored for the emergence of antibiotic-resistant strains during treatment of melioidosis.

Comparison of dexamethasone and lovastatin (mevinolin) as growth inhibitors in cultures of T-cell derived human acute leukemia lines (CEM)

Because previous studies have shown that a reduction of cholesterol synthesis is one of the earliest effects of dexamethasone on neoplastic lymphoid cells, a study was made to compare dexamethasone to lovastatin, a specific inhibitor of cholesterol synthesis, which acts on 3-hydroxy-3-methylglutaryl coenzyme A reductase. Two cell lines were used, both derived from human acute T-cell leukemia, one dexamethasone-sensitive (CEM-C7), the other dexamethasone-resistant (CEM-CI). The results revealed a similar pattern of resistance and sensitivity of both lines to lovastatin, although only the dexamethasone effect was reversed by 1 μM RU 486, the antiglucocorticoid steroid. The cell killing by dexamethasone and lovastatin had the characteristics of apoptosis.