Iso-Sensitest Agar Research Articles

Binding of human clusterin by Staphylococcus epidermidis.

To hypothesise that Staphylococcus epidermidis may possess clusterin receptor(s), bacterial binding of human clusterin was determined. In a fluid phase, the binding was markedly influenced by culture medium and three out of 12 S. epidermidis strains grown on ISO-sensitest agar expressed clusterin-binding ability. S. epidermidis J9P, selected for further study, showed saturable binding of iodine-labelled clusterin, and the binding was only inhibited by unlabelled clusterin. The binding was sensitive to protease treatment. Scatchard plot indicated one single class of binding sites (K(d)=104.2 nM). None of the S. epidermidis strains bound immobilised clusterin. These data imply that ligand-receptor interaction exists between S. epidermidis and clusterin in fluid phase, but the domain(s) recognised by bacteria may have been occluded when clusterin was adsorbed on a surface.

Susceptibility of pneumococci to evernimicin: effect of CO2 and different methodologies

Accurate determination of the antibiotic susceptibility of pathogens is essential for both patient management and epidemiologic purposes. Unfortunately, there are differences in methodology (e.g. media, inoculum, incubation conditions) and interpretation (e.g. numerical values of breakpoint concentrations and zone sizes) between recommendations approved by various organizations. Results using different methods have not been correlated for all antibiotics. Such differences appear to be of particular importance in the case of pneumococci, as incubation in the presence of CO2 is recommended by some but not all testing protocols. For example, incubation in CO2 is recommended by the NCCLS and BSAC for agar diffusion [1,2], by the Swedish guidelines [3] and for the E test [4]. On the other hand, incubation in air is suggested by the NCCLS for broth dilution [5], and by BSAC for agar dilution [6]. The European Committee [7] advises the use of CO2 only when ‘necessary’, while French guidelines [8] do not address this problem. CO2 is a well recognized confounding factor in susceptibility testing, as, among other factors, the reduction in pH it engenders may significantly alter the apparent activity of some antibiotics. Thus, ideally it should be used routinely only when absolutely necessary for the growth of the organism being tested (e.g. for gonococci), which, notwithstanding the recommendationsmentioned above, is not the case for pneumococci.We have recently found (unpublished) that only six of 175 freshly isolated strains of pneumococci (3.4%) were strictly capnophilic. We wish to illustrate discrepancies that can arise between results obtained using different methods, giving as an example comparative data recently obtained with evernimicin, a member of the orthosomycin family of polysaccharide antibiotics [9]. MICs determined by plate dilution were compared with results of E tests, using different media and incubation conditions, as recommended by the NCCLS, the BSAC and AB Biodisk (the manufacturers of the E test). Evernimicin has been shown to diffuse too poorly to be tested by the standard disk diffusion method [10]. MICs of evernimicin (SCH 27899, kindly supplied by the Schering Plough Research Institute) against 50 clinical isolates of Streptococcus pneumoniae were determined by four different methods: agar dilution, according to NCCLS and BSAC recommendations, and E test using Mueller–Hinton agar (MHA) and IsoSensitest agar (ISA). In addition, the effect of CO2 on the activity of evernimicin was investigated by testing 20 of the strains on MHA incubated in CO2 (i.e. standard NCCLS conditions) and in air. Results of E tests were read using an endpoint of 80% inhibition, as recommended by Marshall et al [11]. Media were obtained from Unipath Ltd, Basingstoke, UK. The control strain was S. pneumoniae ATCC 49619, as recommended by the NCCLS [5]. Table 1 shows that MICs obtained using the BSAC method were almost double those determined according to the NCCLS protocol. This difference can be explained by the effect of CO2—present in the test conducted following NCCLS guidelines, absent when using the BSACmethod. From Table 2 it can be seen that under otherwise identical conditions, incubation in CO2 causes a two-fold reduction in the MIC of evernimicin. Marshall et al [11] and Jones and Barrett [12] have, respectively, shown that MICs for pneumococci in MH medium incubated in CO2 are virtually identical in broth and agar, and our results (Table 1) agree very closely with those of the latter workers. The results of E tests in the different media (both carried out in the presence of CO2) were almost identical, but consistently lower than the respective results obtained by the dilution method. A partial explanation of this may be that, as recommended, E test endpoints were read at 80% inhibition, whereas the plate MIC was read, as customary, at 100% inhibition. However, there was little or no discrepancy between E test and plate dilution results when staphylococci and enterococci were tested in a similar manner (unpublished results), so this may be a phenomenon peculiar to pneumococci. It is not clear which of theMIC values obtained is ‘correct’ in terms of prediction of therapeutic efficacy. The results here

Use of indirect conductimetry to establish predictive no effect concentrations of oxytetracycline and oxolinic acid in aquatic sediments

A method based on indirect conductimetry was developed for detecting the minimum effect concentration (MEC) of oxytetracycline and oxolinic acid on the metabolic activity of the microflora of freshwater sediments. For each agent, three repeat examinations of separate samples collected from the same river location generated identical MEC values (20 mg/kg for oxytetracycline and 0.63 mg/kg for oxolinic acid). Sediment microcosms were employed to determine the impact of these agents on the frequency of resistance in the culturable microflora. The minimum concentration capable of selecting for increased frequencies of resistance (MSC) was determined from resistance profiles constructed by measuring the percentage of resistant colony forming units over a range of selective concentrations. For each agent, the MSC values calculated in three independent analyses were identical to the previously determined MEC values. Comparisons of the resistance profiles generated from impacted and unimpacted microcosms allowed the establishment of empirically justifiable breakpoint concentrations for incorporation into Iso-Sensitest agar. These were 12.5 mg/l for oxytetracycline and 1.56 mg/l for oxolinic acid. Arguments are presented that the determination of MEC values for any sediment will allow the determination of no-effect concentrations that can be used in predictive environmental impact studies.

Study to assess the reliability of a disc diffusion method for determining the sensitivity of Gram-positive pathogens to dalfopristin/quinupristin

A standardized method of disc testing the sensitivity of gram-positive pathogens to dalfopristin/quinupristin was developed, and then 'field tested' in ten centres in the UK. For a 15 microg disc, zone diameter breakpoints of 20 mm and 15 mm are suggested when organisms are tested on Iso-Sensitest agar and Iso-Sensitest agar supplemented with 5% whole horse blood, respectively.

Antibiotic Susceptibility Testing (Agar Disk Diffusion and Agar Dilution) of Clinical Isolates of Enterococcus faecalis and E. faecium: Comparison of Mueller-Hinton, Iso-Sensitest, and Wilkins-Chalgren Agar Media

Forty-two isolates of Enterococcus faecalis and 56 isolates of Enterococcus faecium, including 8 vancomycin-resistant strains, were examined for comparative susceptibility to 27 antimicrobial drugs with the agar dilution method, employing Mueller-Hinton (MHA), Iso-Sensitest (ISTA), and Wilkins-Chalgren (WCA) agar. The Bauer-Kirby agar disk diffusion method was used to comparatively test 24 of the agents in parallel. The enterococci yielded better growth on ISTA and WCA. However, WCA completely antagonized co-trimoxazole and, though less, fosfomycin. Importantly, WCA slightly reduced the activities of teicoplanin (minimal inhibitory concentrations, MICs, raised up to twofold) and vancomycin (MICs raised two- to fourfold) against enterococci and staphylococcal quality control strains. Therefore, WCA was judged unsuitable for susceptibility testing of enterococci. For E. faecalis no discrepancies between agar dilution MICs and inhibition zone diameters were encountered with augmentin, ampicillin, ampicillin-sulbactam, chloramphenicol, mupirocin, oxacillin, teicoplanin, and co-trimoxazole. Overall, MHA yielded fewer very major (category I) and major (category II) discrepancies than ISTA. However, numerous minor (category III), slight (category IV), minimal (category V), and/or negligible (category VI) discrepanices were encountered with ciprofloxacin, doxycycline, erythromycin, fosfomycin, fusidic acid, meropenem, ofloxacin and rifampin. With respect to E. faecium, only cefotaxime, mupirocin, oxacillin, and teicoplanin yielded nondiscrepant results. Several very major (I) and major (II) discrepancies were observed with augmentin, ampicillin, ampicillin-sulbactam, doxycycline, fusidic acid, imipenem, and penicillin G. Minor discrepancies (categories III–VI) were particularly numerous with augmentin, chloramphenicol, ciprofloxacin, doxycycline, and piperacillin. The largest numbers of negligible (VI) discrepancies were noted with fosfomycin, fusidic acid, and ofloxacin. It is recommended to test one cephalosporin (cefuroxime or the like) in parallel for educational purposes and to exclude fosfomycin, fusidic acid, and rifampin from test batteries because of the wide scatter of test results. The large number of minimal (V) discrepancies of ciprofloxacin against E. faecalis, the numerous minor (III) and slight (IV) discrepancies of chloramphenicol against E. faecium, and the not insignificant number of very major (I) and minor (III) discrepancies observed with meropenem against isolates of E. faecalis necessitated proposals for new disk intermediate susceptibility criteria.

Towards the establishment of a breakpoint concentration for the determination of resistance to oxolinic acid in marine microflora

A rational framework is presented for establishing valid breakpoint concentrations to be employed in determining the frequency of oxolinic acid resistant bacteria in marine environments. There is a shortage of relevant data concerning the sensitivities of truly marine fish pathogens and, therefore, quantitative estimates of appropriate breakpoints have been made by reference to data on the sensitivity of Aeromonas salmonicida. The use of these data may limit the general applicability of the breakpoints established. Consideration of clinical, pharmacokinetic and microbiological data indicate that the incorporation of 0.5 μg/ml oxolinic acid in Tryptone Soya Agar (TSA) would provide a suitable breakpoint for selecting resistant strains of A. salmonicida. Arguments are presented that the media currently being employed in studies of the frequency of resistance in the vicinity of marine fish farms are inappropriate. It is suggested that media specifically formulated for work with antimicrobial agents, such as Iso-Sensitest Agar (ISA) and Mueller Hinton Agar (MHA) would be more suitable. Seawater is routinely added to media used to enumerate bacteria from the marine environment. The ions present in seawater, particularly Mg 2+ and Ca 2+, inhibit the antimicrobial activity of oxolinic acid. When 70% artificial seawater is used in preparing ISA, the median percentage bioactivity of oxolinic acid is approximately 4.5%. Thus, in this medium oxolinic acid concentrations of 10–12 μg/ml will exert a selection equivalent to that exerted by 0.5 μg/ml in standard TSA media.

The effect of a combination of Iso-Sensitest agar and ampicillin on the detection of enterobacter beta-lactamase.

The ampicillin MICs for faecal strains of E. cloacae (n = 11) and Enterobacter species not identified to species level (n = 3) were noticed to be two-fold to four-fold lower on Iso-Sensitest than on Mueller-Hinton II agar. The levels of inducible beta-lactamase on Iso-Sensitest, Mueller-Hinton, and a selective MacConkey-based agar, with and without ampicillin, were determined. The level produced on Iso-Sensitest with ampicillin was comparable to that induced by Mueller-Hinton alone. We conclude that when routine procedures for the detection of beta-lactamase-based resistance are evaluated, not only should care be taken to choose the right antibiotics, but also different combinations of beta-lactams and agar should be tested.

Antimicrobial susceptibility testing of 230 Helicobacter pylori strains: importance of medium, inoculum, and incubation time.

No standardized method of susceptibility testing for Helicobacter pylori is currently available, so before a large agar dilution study comprising 230 H. pylori strains belonging to more than 80 genetically different groups was initiated, we performed a relatively small preliminary study to determine the influences of medium, inoculum density, and incubation time. Seven media were investigated and were primarily evaluated on the basis of their abilities to support growth both semiquantitatively and qualitatively; Iso-Sensitest agar supplemented with 10% horse blood was found to be well suited for the purpose; this was closely followed by Mueller-Hinton agar with 10% horse blood, Mueller-Hinton with 10% sheep blood, and finally, 7% lysed horse blood agar. Investigations of two inoculum densities and two incubation times resulted in recommendations for the use of 10(9) CFU/ml (10[6] CFU/spot) as the inoculum and 72 h as the incubation time. A modest inoculum effect was noted for amoxicillin and metronidazole. By the methodology derived from our preliminary study, the susceptibilities of 230 H. pylori strains to six antibiotics were subsequently determined. The results were generally in accord with those of others, and apart from metronidazole, the MIC of which for approximately 25% of the strains tested was >8 microg/ml, resistance was low in Denmark. The situation might, however, quickly change when and if the number of indications for antibiotic therapy for H. pylori infections increase. Consequently, susceptibility testing of all H. pylori strains is recommended in order to survey the development of resistance, and in our hands the described methodology was relatively easy to perform and the results were easy to read.

Evaluation of different methods for the detection of methicillin resistance in coagulase-negative staphylococci.

The efficacy of 19 agar diffusion methods for the detection of methicillin resistance among coagulase-negative staphylococci (CoNS) within 24 h was evaluated. A total of 359 CoNS isolates were tested, of which 204 were Staphylococcus epidermidis. In 164 isolates, the presence of mecA was investigated; 61 strains were mecA-positive and 103 were mecA-negative by Southern blot analysis. Based on the best agreement shown with the mecA determination (94%) among four agar dilution assays for determining methicillin MIC, an assay with Columbia agar supplemented with NaCl and incubation with a heavy bacterial inoculum of 10(5)-10(6) cfu/spot was used as the reference MIC method. The best agar diffusion results were obtained with a 1 microg oxacillin disc on Columbia agar with 4.5% NaCl supplement. With this method, 99% of S. epidermidis and 94% of non-S. epidermidis were in agreement with the MIC determination. However, Columbia (without NaCl), Mueller-Hinton and Isosensitest agars were almost as useful when a 1 microg oxacillin disc was used. The zone breakpoints for S. epidermidis were, in general, considerably larger than those for other CoNS species and, consequently, differentiation according to species is recommended. Furthermore, resistance to other antibiotics, such as gentamicin and erythromycin, makes methicillin resistance highly likely.

Susceptibility testing of Stenotrophomonas maltophilia to carbapenems.

The susceptibility of 20 clinical isolates of Stenotrophomonas maltophilia to the carbapenems imipenem and meropenem was investigated by various methods. S. maltophilia appeared sensitive to meropenem but resistant to imipenem by disc testing in Iso-sensitest agar. Agar dilution MICs were performed using Iso-sensitest agar and with incubation under three sets of atmospheric conditions. MICs of meropenem were considerably lower than those of imipenem; this effect was maximal after incubation in 5% CO2 when the MIC of meropenem was approximately 64 times less than that of imipenem. Induction experiments showed that both carbapenems could induce production of the L1 carbapenemase. However, disc approximation tests showed that imipenem could induced resistance to meropenem. Partially stably derepressed mutants were readily selected in vitro. We conclude that, although S. maltophilia may give large zones of inhibition to meropenem on disc testing, resistant mutants are readily selected and therefore standard sensitivity tests may be poorly predictive of clinical outcome of treatment of S. maltophilia infections with meropenem.

Multi-centre collaborative study for the in vitro evaluation of new macrolides dirithromycin and erythromycylamine

A national study was conducted to determine the in vitro activity of 2 newer macrolides, dirithromycin and erythromycylamine compared with that of erythromycin, tetracycline and penicillin. Nineteen major teaching hospitals participated in the study. Minimal Inhibitory Concentrations (MICs) were determined by agar dilution, mostly using Iso-Sensitest Agar and an inoculum of 10(4) cells per spot. 2284 clinically significant strains were isolated in late 1991 and early 1992, comprising 1736 Gram-positive cocci, 355 Haemophilus influenzae, 97 Moraxella catarrhalis, 32 Listeria monocytogenes, 25 Neisseria meningitidis and 39 Neisseria gonorrhoeae were tested. The study indicates that dirithromycin and erythromycylamine possess antibacterial activity equivalent to that of erythromycin against most Gram-positive cocci and M. catarrhalis. Strains resistant to erythromycin were also resistant to dirithromycin and to erythromycylamine. Tetracycline was as active as the macrolides against both penicillin-resistant and penicillin-susceptible strains of Staphylococcus aureus. Coagulase-negative penicillin-resistant staphylococci, compared with tetracycline, were relatively resistant to the macrolides. H. influenzae was less susceptible than the Gram-positive cocci.

Evaluation of E test as a rapid method for determining MICs for nutritionally variant streptococci

E test was evaluated as an alternative rapid and simple method of MIC estimation for nutritionally variant streptococci. E test with various media was compared with conventional broth and plate dilution techniques supplemented with 0.001% (wt/vol) pyridoxal hydrochloride (vitamin B6). Of the 14 strains tested with E test, isosensitest agar supplemented with 5% defibrinated horse blood and 0.001% pyridoxal HCl, with and without 0.01% cysteine, gave complete agreement within one twofold-dilution titer of the agar reference method and between 93 and 86% agreement within one twofold-dilution titer of the broth reference method. E test MICs with other media were comparable; however, these were considerably more difficult to interpret. Use of Mueller-Hinton and Columbia-based supplemented agar showed hazy growth and double zoning around the endpoint, respectively. The addition of 0.01% (wt/vol) cysteine to media exhibited no significant effect, and incubation in 5% carbon dioxide (CO2) did not affect MICs.

Estudio comparativo del agar Iso-Sensitest y el agar Mueller-Hinton

710 strains of bacteria from different specimens were studied in order to compare the zone sizes of inhibition from the lso-Sensitest agar and Mueller- Hinton agar. The disk diffusion technique of the NCCLS (National Commiitee for Clinical Laboratory Standards) was used. Statistically, using chisquare analysis for the specimens under observation, a reliability of 99% was obtained, therefore, there is no significant difference between the two media. In Iso-Sensit est agar, greater clarity was obtained for the diameters of inhibition halos; 62.0% better readings or greater visibility of inhibition zones was observed with cultures such as Enterococcus sp., Staphylococcus aureus showed up more sharply in 21.4% and Providencia stuartil in 20.0% flasks.

The induction of trimethoprim resistance encoded by the type IV dihydrofolate reductase gene.

The effect of plasmid pUK1123, which confers low level resistance to trimethoprim when tested on solid minimal medium, but also no resistance when tested on IsoSensitest agar, was investigated in liquid media. The growth of Escherichia coli J62-2, harbouring pUK1123, was unaffected in liquid minimal medium containing trimethoprim 10 mg/L. However, in IsoSensitest broth, exposure to this drug concentration resulted in bacteriostasis. After an initial delay, resistance to trimethoprim was induced in IsoSensitest broth containing trimethoprim 10 mg/L, by the imposition of thymine starvation. This response was immediately reversible when trimethoprim was removed, confirming that resistance resulted from induction rather than selection of resistant mutants.

Comparison of an HPLC and bioassay method to determine antimicrobial concentrations after intravenous and oral administration of enrofloxacin in four dogs

Plasma samples of dogs given 5 mg kg −1 bodyweight of a broad spectrum antimicrobial with the active ingredient enrofloxacin were assayed by two different methods (bioassay: Escheriehia coli 14 ICB 4004 on iso sensitest agar; high performance liquid chromatography with a RP C18 column). At concentrations up to 1000 ng ml −1 a linear correlation between values obtained by the two assay methods was found. At concentrations above 1000 ng ml −1 no correlation could be determined. The main metabolite of enrofloxacin, ciprofloxacin, is an important determinant of overall antimicrobial activity and hence influences bioassay results.

The influence of anaerobiosis on the activity of fosfomycin trometamol.

MICs of fosfomycin trometamol were estimated for 40 strains of bacteria (20 gram-positive cocci, 20 gram-negative bacilli) by the agar incorporation method (Iso-Sensitest agar) in the presence of the potentiating agent, glucose-6-phosphate (25 mg/l). Titrations were carried out in duplicate under aerobic and anaerobic conditions. For 22 strains (12 gram-negative bacilli), a fourfold or greater reduction in MIC was observed in tests conducted under anaerobic conditions. The effect was particularly marked with Klebsiella spp., four of five strains of which showed a 16- to 32-fold reduction in MIC in anaerobic conditions. To investigate the reasons for the effect of anaerobiosis, selected strains were examined in an opacity monitoring device in which cultures can be grown in aerobic or anaerobic atmosphere. Surprisingly, the effect of anaerobiosis observed by continuous turbidimetric monitoring was much less than that seen in agar incorporation MIC titrations: under anaerobic conditions, there was little or no reduction in the concentration of fosfomycin trometamol required to cause a lytic effect on dense bacterial cultures, and a small, but variable effect on the emergence of resistant variants.

In-vitro activity of RP 59500, a new semisynthetic streptogramin antibiotic, against gram-positive bacteria.

A study of the in-vitro activity of RP 59500, a semisynthetic derivative of pristinamycin, against a range of Gram-positive bacteria including erythromycin-resistant strains was undertaken. MICs were determined by plate dilution in IsoSensitest agar and MBCs by velvet pad replication. RP 59500 was found to have in-vitro activity almost identical to that of its parent compound, pristinamycin. Sixty methicillin-resistant Staphylococcus aureus (MRSA) and 60 methicillin-sensitive S. aureus (MSSA) were found to be sensitive to RP 59500, with MICs of 0.13-1 mg/L. All the MSSA and most MRSA showed an MBC less than 2 mg/L. Erythromycin-resistant S. aureus (62) were as sensitive to RP 59500 as were erythromycin-sensitive strains (58). RP 59500 was more active against MRSA than fusidate, vancomycin, amikacin, ciprofloxacin, imipenem or erythromycin. Forty strains of coagulase-negative staphylococci (11 were erythromycin-resistant) showed MICs of 0.25-1 mg/L, and RP 59500 was more active than methicillin, erythromycin, imipenem, cefotaxime or vancomycin. Sixty strains of streptococci (20 pneumococci and 40 of groups A, B, C, or G) and 20 enterococci were inhibited by 0.13-1 mg/L and 0.25-4 mg/L, respectively. Gram-positive bacilli (five each of diphtheroids, lactobacilli, Listeria monocytogenes and Bacillus spp., and 19 Clostridium spp.) were also sensitive, with MICs of between 0.06 and 4 mg/L. All 279 strains tested were judged to be sensitive to RP 59500, which was bactericidal and showed a small inoculum effect. The activity against MRSA, and against erythromycin-resistant strains of all species was particularly interesting.

Susceptibility to -lactam antibiotics of mutant strains of Xanthomonas maltophilia with high- and low-level constitutive expression of L1 and L2 -lactamases

Xanthomonas maltophilia produces two inducible beta-lactamases, L1 and L2, and resists the antimicrobial activity of beta-lactam antibiotics, including carbapenems. L1 is a zinc-metaloenzyme with carbapenemase activity; L2 is an unusual cephalosporinase. Mutant strains with high- and low-level constitutive expression of these enzymes were derived from three reference strains of X. maltophilia. With a single exception, the mutant strains had altered expression of both enzymes, indicating that these beta-lactamases share regulatory components. The exception was a mutant strain that had low-level constitutive (basal) expression of L1 enzyme but remained inducible for L2. A parent strain with low-level beta-lactamase inducibility was more susceptible to penicillins, cephalosporins and carbapenems than were those in which higher levels of enzyme activity were inducible. Mutations that caused high-level constitutive beta-lactamase expression increased resistance to penicillins and newer cephalosporins. beta-Lactamase basal mutant strains, including the one that remained inducible for L2 enzyme, were more susceptible than inducible strains to these drugs. Organisms with inducible or high-level constitutive beta-lactamase expression were equally resistant to meropenem and imipenem but basal mutant strains, including the one that remained inducible for L2 enzyme, were more susceptible to meropenem than imipenem. Minimal inhibitory concentrations of meropenem, penicillins and cephalosporins, but not imipenem, were greater on Mueller Hinton agar than on IsoSensitest or Diagnostic Sensitivity Test agars. This behaviour was independent of beta-lactamase inducibility, and may reflect permeability differences between cells grown on different media.

An Evaluation of the Antibacterial Activities of Combinations of Sulfonamides, Trimethoprim, Dibromopropamidine, and Silver Nitrate Compared with Their Uptakes by Selected Bacteria

Modifications of antibacterial activity have been demonstrated using combinations of two antibacterials from trimethoprim, sulfonamides (sulfadiazine, sulfamerazine, and silver sulfadiazine), silver nitrate, and dibromopropamidine isethionate, either formulated in a cream base or dissolved in peptone water. The creams were evaluated using the agar cup diffusion method in isosensitest agar. The peptone water solutions provided fractional inhibitory concentrations for combinations of the antibacterial substances. The test organisms were Pseudomonas aeruginosa, Enterobacter cloacae, and Staphylococcus aureus Bacterial uptakes of antibacterial combinations, determined by either an HPLC assay method or an atomic absorption method, combined with dry cell weight determinations, indicated that enhancement of activity of the antibacterial combinations against P. aeruginosa (two strains) and E. cloacae were related to marked increases in the bacterial uptake of the chemical agents. Decreases in activity were related to decreased uptake of either dibromopropamidine and/or silver ions. The effect of the trimethoprim and the sulfonamides was shown to depend on their effect on bacterial folate synthesis. It is suggested that partial blockade of the folate synthetic pathway leads to an effect on cell permeability which results in increased uptake of antibacterials. Dibromopropamidine isethionate also has an effect on cell permeability which produces an increased bacterial uptake of a second antibacterial present in the medium. These findings provide further explanation of how subinhibitory concentrations of trimethoprim and sulfonamide combinations are synergistic against a wide range of bacteria even when certain bacteria are resistant to either member of the combination.

Problems with Iso-Sensitest agar

Journal Article Problems with Iso-Sensitest agar Get access J. M. ANDREWS, J. M. ANDREWS Department of Medical Microbiology, Dudley Road HospitalBirmingham B18 7QH, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar R. WISE R. WISE Department of Medical Microbiology, Dudley Road HospitalBirmingham B18 7QH, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Antimicrobial Chemotherapy, Volume 27, Issue 6, June 1991, Page 868, https://doi.org/10.1093/jac/27.6.868 Published: 01 June 1991