Biomedical subjects

E K Manavathu

Publications and source records attributed to E K Manavathu.

At least 19 recordsLinked to original sources

PubMed2003

Cytotoxic 4'-aminochalcones and related compounds.

A series of 4'-aminochalcones 1 and related maleamic acids 2 and Schiff bases 3 were designed and synthesized as candidate cytotoxic agents. The atomic charges on different atoms of representative compounds were calculated. Evaluation of the enones 1-3 against human Molt 4/C8 and CEM T-lymphocytes as well as murine P388 and L1210 leukemic cells revealed that approximately 40% of the IC50 values generated were less than 10 microM. In some cases cytotoxicity was correlated with the Hammett sigma values of the aryl substituents and less frequently with the aryl Hansch pi values. Evidence was obtained that in general these compounds displayed selective toxicity for certain malignant cells and were well tolerated in mice. This study has revealed various directions whereby the project may be amplified in the future with a view to finding compounds with increased cytotoxicity to tumour cells.

Animals↗

PubMed2002

Caspofungin.

Available systemically effective antifungal agents for the treatment of invasive fungal infections are few. With the increasing recognition of a need for newer antifungal drugs, caspofungin has been introduced as the first member of a new class of compounds called echinocandins. This paper reviews the chemistry and mechanism of action of caspofungin, its activity in vitro and in animal models, and clinical pharmacokinetics,clinical efficacy and safety in patients.

Animals↗

PubMed2001

A conformational and structure-activity relationship study of cytotoxic 3,5-bis(arylidene)-4-piperidones and related N-acryloyl analogues.

A series of 3,5-bis(arylidene)-4-piperidones 1 and related N-acryloyl analogues 2 were prepared as candidate cytotoxic agents with a view to discerning those structural features which contributed to bioactivity. A number of the compounds were markedly cytotoxic toward murine P388 and L1210 leukemic cells and also to human Molt 4/C8 and CEM neoplasms. Approximately 40% of the IC50 values generated were lower than the figures obtained for melphalan. In virtually all cases, the N-acyl compounds were significantly more bioactive than the analogues 1. In general, structure-activity relationships revealed that the cytotoxicity of series 1 was correlated positively with the size of the aryl substituents, while in series 2, a -sigma relationship was established. In particular, various angles and interatomic distances were obtained by molecular modeling, and the presence of an acryloyl group on the piperidyl nitrogen atom in series 2 affected the relative locations of the two aryl rings. This observation, along with some differences in distances between various atoms in series 1 and 2, may have contributed to the disparity in cytotoxicity between 1 and 2. The results obtained by X-ray crystallography of representative compounds were mainly in accordance with the observations noted by molecular modeling. Selected compounds interfered with the biosynthesis of DNA, RNA, and protein in murine L1210 cells, while others were shown to cause apoptosis in the human Jurkat leukemic cell line. This study has revealed the potential of these molecules for development as cytotoxic and anticancer agents.

Acrylates↗

PubMed2001

Aspergillus: rising frequency of clinical isolation and continued susceptibility to antifungal agents, 1994-1999.

We investigated the frequency of clinical isolation and the in vitro susceptibility to antifungal agents of Aspergillus species obtained from patients at the Detroit Medical Center from January 1994 to December 1999. During this period, 593 clinical isolates of Aspergillus species [406 A. fumigatus, 68%; 82 A. niger, 14%; 42 A. flavus, 7%; 63 Aspergillus spp., 11%] were recovered from hospitalized patients. From January 1996 to December 1999, approximately 2.5-4.5 fold yearly increase of the number of aspergillus isolates occurred compared to that of 1994. Conidial suspensions from clinical isolates were prepared and their in vitro susceptibility to amphotericin B and three azoles were determined. All four agents examined were extremely active. The minimum inhibitory concentrations (MIC(90)) (microg/mL) of amphotericin B, itraconazole, voriconazole and posaconazole for A. fumigatus (n = 406) were 0.5, 1.0, 0.5 and 0.25. Similar values were noted for non-A. fumigatus isolates. A year-to-year comparison of the MIC(90) of the four agents for A. fumigatus and non-A. fumigatus isolates over the 6-year study period showed no significant differences. Our study showed a steady increase in the frequency of clinical isolation of Aspergillus species; and the organism has remained susceptible to amphotericin B/triazoles without any change in susceptibility levels during the 6-year study period.

Amphotericin B↗

PubMed2001

Isolation and in vitro susceptibility to amphotericin B, itraconazole and posaconazole of voriconazole-resistant laboratory isolates of Aspergillus fumigatus.

OBJECTIVES: To select voriconazole-resistant mutants of Aspergillus fumigatus in the laboratory from drug-susceptible clinical isolates and examine their in vitro susceptibility to amphotericin B and investigational azoles, and to compare the intramycelial accumulation of voriconazole in the resistant isolates with that in the susceptible parent. METHODS: Voriconazole-resistant Aspergillus fumigatus isolates were selected in the laboratory from three highly susceptible (MIC < or = 0.5 mg/L) clinical isolates by stepwise selection on peptone yeast extract glucose (PYG) agar containing 0.5 mg and 4 mg voriconazole/L. Twenty-three colonies that grew in the presence of 4 mg voriconazole/L on PYG agar (frequency 1.9 x 10(-8)) were tested for their in vitro susceptibility to amphotericin B, itraconazole, voriconazole and posaconazole by a broth macrodilution technique. The accumulation of voriconazole in the mycelia of two representative resistant isolates (VCZ-W42 and VCZ-W45) was determined by a previously described bioassay. RESULTS: The geometric mean MICs (mg/L) of amphotericin B, itraconazole, voriconazole and posaconazole for these isolates were 0.45 +/- 0.19, 0.69 +/- 0.45, 5.24 +/- 3.74 and 0.27 +/- 0.18, respectively. A comparison of the geometric mean MICs of the antifungals obtained for the resistant isolates to those of the susceptible parents showed 1.15-, 2.76-, 16.90- and 1.42-fold increases, respectively, for amphotericin B, itraconazole, voriconazole and posaconazole, suggesting that low-level cross-resistance exists between the azole antifungals. The susceptible parent and the resistant isolates accumulated similar amounts of voriconazole. CONCLUSIONS: These results suggest that spontaneous mutants of Aspergillus fumigatus resistant to voriconazole could emerge among clinical isolates under selection pressure and that the observed reduced in vitro susceptibility to voriconazole may not be due to reduced accumulation of the drug in the mycelia.

Amphotericin B↗

PubMed2001

Inhibition of H(+)-ATPase-mediated proton pumping in Cryptococcus neoformans by a novel conjugated styryl ketone.

We investigated the in vitro susceptibility of clinical isolates of Cryptococcus neoformans to the novel conjugated styryl ketone NC1175 by broth microdilution. The MIC(90) and the MFC of NC1175 for C. neoformans were 1 and 2 mg/L, respectively. NC1175 at low concentrations (1-4 mg/L) completely inhibited the glucose-induced acidification of the external medium caused by the extrusion of intracellular protons mediated by the plasma membrane located H(+)-ATPase. These data suggest that NC1175 is a fungicidal agent for C. neoformans and its possible cellular target(s) include the H(+)-ATPase.

Antifungal Agents↗

PubMed2000

Proton translocating ATPase mediated fungicidal activity of a novel complex carbohydrate: CAN-296.

CAN-296 is a complex carbohydrate (approximately 4300 Da) isolated from the cell wall of Mucor rouxii. It exhibits excellent in vitro fungicidal activity against a wide spectrum of pathogenic yeasts, including isolates resistant to azoles and polyenes. The rapid irreversible action of CAN-296 on intact fungal cells and protoplasts suggested a membrane-located target for its action. The proton translocating ATPase (H+-ATPase) of fungi is an essential enzyme required for the regulation of intracellular pH and nutrient transport. Inhibition of H+-ATPase leads to intracellular acidification and cell death. We therefore investigated the effect of CAN-296 on H+-ATPase-mediated proton pumping by intact cells of Candida and Saccharomyces species by measuring the glucose-induced acidification of external medium. CAN-296 inhibited proton pumping of Candida albicans, Candida glabrata, Candida krusei, Candida guilliermondii and Saccharomyces cerevisiae at low concentrations (0.078-1.25 mg/l). Other commonly used antifungal agents such as amphotericin B, itraconazole and fluconazole had no effect on H+-ATPase-mediated proton pumping. A clinical isolate of C. glabrata with reduced in vitro susceptibility (MIC = 10 mg/l) to CAN-296 also showed resistance to CAN-296 inhibition of proton pumping. Purified membrane fractions rich in H+-ATPase activity were not inhibited by CAN-296 suggesting that the effect on the H+-ATPase-mediated proton pumping in intact yeast cells is an indirect effect, perhaps mediated by local or global disruption of the plasma membrane. These results suggest that the inhibition of fungal H+-ATPase is at least partly responsible for the antifungal activity of CAN-296.

Adenosine Triphosphate↗

PubMed2000

A comparative study of the in vitro susceptibilities of clinical and laboratory-selected resistant isolates of Aspergillus spp. to amphotericin B, itraconazole, voriconazole and posaconazole (SCH 56592).

We investigated the in vitro susceptibilities of clinical and laboratory-selected Aspergillus spp. to posaconazole, and compared the results with those obtained for amphotericin B, itraconazole and voriconazole. Conidial suspensions from clinical isolates (284 Aspergillus fumigatus, 66 Aspergillus niger, 31 Aspergillus flavus and 43 Aspergillus spp.) and laboratory-selected resistant A. fumigatus isolates (15 resistant to amphotericin B, 25 to itraconazole and 12 to voriconazole) were prepared and their susceptibilities to various antifungal agents determined using a previously described broth macrodilution technique. The geometric mean MICs (mg/L) of posaconazole for A. fumigatus (0.17 +/- 0.11) and non-A. fumigatus aspergilli (0.16 +/- 0.28) were significantly lower (P 0.05) than those for amphotericin B, itraconazole and voriconazole. Amphotericin B-resistant A. fumigatus isolates were as susceptible to posaconazole as the parental strain. Itraconazole- and voriconazole-resistant isolates showed low-level (two- to three-fold increase in MICs) cross-resistance to posaconazole. The minimum fungicidal concentrations (mg/L) of posaconazole for A. fumigatus (n = 58) and non-A. fumigatus aspergilli (n = 40) were 4. 45 +/- 2.70 (range 0.25-8) and 4.14 +/- 3.03 (range 0.5-8), respectively. Time-kill studies showed that the fungicidal activity of posaconazole against A. fumigatus is time- and concentration-dependent (for example, posaconazole 4 mg/L killed >99% of A. fumigatus conidia within 24 h). These results suggest that overall, posaconazole has better activity and a smaller range of MICs for Aspergillus spp., including those with reduced susceptibility to amphotericin B, itraconazole and voriconazole.

Amphotericin B↗

PubMed1999

In vitro susceptibilities of Aspergillus species to voriconazole, itraconazole, and amphotericin B.

We studied the in vitro activity of voriconazole (VCZ) itraconazole (ITZ) and amphotericin B (AMB) against 216 clinical isolates of Aspergillus spp. (142 Aspergillus fumigatus and 74 nonfumigatus Aspergillus spp. isolates) using a broth macrodilution method. The MICs (microgram/mL) (mean, range) for A. fumigatus were: VCZ 0.88, 0.25-4; ITZ 0.54, 0.25-4; AMB 2.16, 0.5-8. MIC90s were: VCZ 2, ITZ 1, AMB 4. MICs for nonfumigatus Aspergillus spp. were: VCZ 1.57, 0.25-4; ITZ 1.74, 0.25-4; AMB 2.88, 0.5-8. MIC90s for this group were: VCZ 4, ITZ 4, AMB 4. We also studied the susceptibility to VCZ of 18 AMB-resistant (mean, MIC 6.0 micrograms/mL) and 28 ITZ-resistant (mean, MIC 13.28 micrograms/mL) A. fumigatus isolates selected in the laboratory. The mean MICs of VCZ were 0.59 microgram/mL for AMB-resistant and 1.32 micrograms/mL for ITZ-resistant isolates. Our study showed that VCZ and ITZ had comparable in vitro activity against the isolates studied, except against A. fumigatus, where the MIC of ITZ was lower. The azoles had better in vitro activity than AMB against A. fumigatus and non-fumigatus spp. The non-fumigatus Aspergillus spp. were less susceptible to all three antifungals evaluated. When tested against ITZ- or AMB-resistant A. fumigatus strains, VCZ retained good activity, showing only a modest rise in the MIC against ITZ-resistant strains.

Amphotericin B↗

PubMed1999

Reduced susceptibility in laboratory-selected mutants of Aspergillus fumigatus to itraconazole due to decreased intracellular accumulation of the antifungal agent.

To study the mechanism of resistance of Aspergillus fumigatus to itraconazole, spontaneous mutants with reduced susceptibility were selected by spreading 2 x 10(8) conidia from a clinical isolate (W73355) susceptible to miconazole (MIC 2 mg/l), itraconazole (MIC 0.25 mg/l) and amphotericin B (MIC 0.5 mg/l) on 40 peptone yeast extract glucose agar plates containing miconazole (32 mg/l). The 19 colonies that grew (frequency 0.95 x 10(-7)) in the presence of miconazole were screened by broth macrodilution technique for their susceptibility to itraconazole. A total of two isolates (frequency 1 x 10(-8)) MCZ14 and MCZ15 had MICs of 16 and 8 mg/l, respectively, for itraconazole. Both MCZ14 and MCZ15 showed concomitant increases in MICs for ketoconazole and miconazole, but not for amphotericin B. Growth inhibition studies as well as kill curve experiments revealed that MCZ14 and MCZ15 were less susceptible to itraconazole compared to the parental strain. The intracellular accumulation of itraconazole in A. fumigatus was time and concentration dependent. Maximum accumulation was obtained within 30 min at 5 microM itraconazole. In MCZ14 and MCZ15 intracellular accumulation of [3H]itraconazole was reduced by approximately 80 and 60%, respectively, compared to the susceptible parent. The respiratory inhibitor carbonyl cyanide m-chlorophenyl hydrazone at 200 microM reduced the intracellular accumulation of itraconazole by approximately 36.2% (P < or = 0.05) in the parent and in the mutant strains. These results suggest that (i) the reduced accumulation of itraconazole in MCZ14 and MCZ15 is due to diminished permeability of the drug and perhaps not due to efflux, (ii) the uptake of itraconazole in A. fumigatus may be an energy dependent process, and (iii) decreased accumulation of itraconazole is at least in part responsible for the reduced susceptibility of the mutant isolates to itraconazole.

Antifungal Agents↗

PubMed1999

Involvement of calcium inhibitable binding to the cell wall in the fungicidal activity of CAN-296.

CAN-296 is a heat stable, complex carbohydrate (molecular mass 4300 Da) isolated from the cell wall of the filamentous fungus Mucor rouxii. It possesses potent in-vitro fungicidal activity against a wide spectrum of pathogenic yeasts, including azole-resistant isolates of Candida albicans and Candida glabrata. As a preliminary step in the study of the mode of action of this novel antifungal agent, we investigated the effect of various cations on the antifungal activity as well as the binding of CAN-296 to intact cells and cell-wall fractions of C. albicans. The antifungal activity of CAN-296 was inhibited by low concentrations of calcium, magnesium and lithium and by high concentrations of barium, cobalt and manganese, but not by potassium and copper. The calcium-mediated inhibition of the antifungal activity of CAN-296 was readily reversible by the removal of calcium by dialysis, and the fungicidal activity of the inhibited compound was fully restored. The uptake/binding of CAN-296 to intact cells and to the cell-wall fraction of C. albicans was time and concentration dependent. Maximum uptake/binding was obtained at 5 mg/L within 60 min and was associated with the aggregation of intact cells. Washing intact cells and the cell-wall fraction preincubated with radiolabelled CAN-296 with 150-fold excess of unlabelled compound failed to remove CAN-296 associated with the intact cells and the cell-wall fraction, suggesting that the binding of CAN-296 to C. albicans is tight. The uptake/binding of CAN-296 and the drug-mediated aggregation of intact cells were inhibited by calcium in a concentration-dependent manner. The fact that CAN-296 is a fungicidal agent that binds to intact cells and the cell-wall fraction of C. albicans very tightly, together with the observation that calcium was able to inhibit the fungicidal activity as well as the uptake/binding of CAN-296, suggests that the mode of action of this novel antifungal agent may involve interaction with the cell wall of C. albicans.

Antifungal Agents↗

PubMed1999

Proton-pumping-ATPase-targeted antifungal activity of a novel conjugated styryl ketone.

NC1175 (3-[3-(4-chlorophenyl)-2-propenoyl]-4-[2-(4-chlorophenyl)vinyle ne]-1- ethyl-4-piperidinol hydrochloride) is a novel thiol-blocking conjugated styryl ketone that exhibits activity against a wide spectrum of pathogenic fungi. Incubation of NC1175 with various concentrations of cysteine and glutathione eliminated its antifungal activity in a concentration-dependent fashion. Since NC1175 is a lipophilic compound that has the potential to interact with cytoplasmic membrane components, we examined its effect on the membrane-located proton-translocating ATPase (H(+)-ATPase) of yeast (Candida albicans, Candida krusei, Candida guilliermondii, Candida glabrata, and Saccharomyces cerevisiae) and Aspergillus (Aspergillus fumigatus, Aspergillus niger, Aspergillus flavus, and Aspergillus nidulans) species. The glucose-induced acidification of external medium due to H(+)-ATPase-mediated expulsion of intracellular protons by these fungi was measured in the presence of several concentrations of the drug. NC1175 (12.5 to 50 microM) inhibited acidification of external medium by Candida, Saccharomyces, and Aspergillus species in a concentration-dependent manner. Vanadate-inhibited hydrolysis of ATP by membrane fractions of C. albicans was completely inhibited by 50 microM NC1175, suggesting that the target of action of NC1175 in these fungi may include H(+)-ATPase.

Adenosine Triphosphate↗

PubMed1999

Comparative study of susceptibilities of germinated and ungerminated conidia of Aspergillus fumigatus to various antifungal agents.

Conidia are used as inocula for the in vitro susceptibility testing of Aspergillus fumigatus. Since the MIC is defined on the basis of visible mycelial growth, conidia should germinate and produce sporelings (germinated conidia) for monitoring of the growth inhibition and fungicidal activity of a drug. If a compound is capable of inhibiting germination of conidia while affecting or not affecting the growth of the organism, the MIC obtained will be the concentration of the drug required for the inhibition of conidial germination but not necessarily that required for inhibition of the growth of the organism. We investigated the susceptibility of germinated and ungerminated conidia to amphotericin B, itraconazole, voriconazole, and SCH56592. The MICs of various antifungal agents for germinated conidia were almost identical to those obtained for ungerminated conidia. In addition, both the germinated and ungerminated conidia were killed with almost equal efficiency by all of the compounds tested when exposed to the drugs for 24 h. These results suggest that either germinated or ungerminated conidia could be used as inocula for in vitro susceptibility studies of A. fumigatus with identical results.

Amphotericin B↗

PubMed1998

Cytotoxic activities of Mannich bases of chalcones and related compounds.

Various Mannich bases of chalcones and related compounds displayed significant cytotoxicity toward murine P388 and L1210 leukemia cells as well as a number of human tumor cell lines. The most promising lead molecule was 21 that had the highest activity toward L1210 and human tumor cells. In addition, 21 exerted preferential toxicity to human tumor lines compared to transformed human T-lymphocytes. Other compounds of interest were 38, with a huge differential in cytotoxicity between P388 and L1210 cells, and 42, with a high therapeutic index when cytotoxicity to P388 cells and Molt 4/C8 T-lymphocytes were compared. In general, the Mannich bases were more cytotoxic than the corresponding chalcones toward L1210 but not P388 cells. A ClusCor analysis of the data obtained from the in vitro human tumor screen revealed that the mode of action of certain groups of compounds was similar. For some groups of compounds, cytotoxicity was correlated with the sigma, pi, or molar refractivity constants in the aryl ring attached to the olefinic group. In addition, the IC50 values in all three screens correlated with the redox potentials of a number of Mannich bases. X-ray crystallography and molecular modeling of representative compounds revealed various structural features which were considered to contribute to cytotoxicity. While a representative compound 15 was stable and unreactive toward glutathione (GSH) in buffer, the Mannich bases 15, 18, and 21 reacted with GSH in the presence of the pi isozyme of glutathione S-transferase, suggesting that thiol alkylation may be one mechanism by which cytotoxicity was exerted in vitro. Representative compounds were shown to be nonmutagenic in an intrachromosomal recombination assay in yeast, devoid of antimicrobial properties and possessing anticonvulsant and neurotoxic properties. Thus Mannich bases of chalcones represent a new group of cytotoxic agents of which 21 in particular serves as an useful prototypic molecule.

Animals↗

PubMed1998

In-vitro isolation and antifungal susceptibility of amphotericin B-resistant mutants of Aspergillus fumigatus.

Aspergillus fumigatus mutants resistant to amphotericin B were selected in the laboratory following UV irradiation. A total of 18 colonies (frequency 1.8 x 10(-7)) that grew in the presence of amphotericin B (8 mg/L and 16 mg/L) on peptone yeast extract glucose agar were tested for their susceptibility to amphotericin B, nystatin, azoles, and the echinocandin L-743872. Ten of the 18 isolates showed an eight-fold rise in amphotericin B MIC (4 mg/L) compared with the susceptible parent whereas the remaining isolates showed a 16 to 32-fold rise in amphotericin B MIC (8-16 mg/L). Subculturing of three representatives from each of the groups that had MIC values of 4 mg/L and 8-16 mg/L for six cycles revealed that the resistance trait was stably expressed. All amphotericin B-resistant isolates showed a significant level of cross-resistance to nystatin but not to azoles and L-743872. Kill-curve studies with amphotericin B revealed that the killing of the resistant isolates was significantly less than that of the susceptible parent strain. These results show that amphotericin B-resistant mutants of A. fumigatus can be isolated in the laboratory following a single-step UV-induced mutagenesis and suggest that similar mechanisms could operate in nature for the emergence of resistance in clinical isolates.

Amphotericin B↗

PubMed1998

In-vitro and in-vivo susceptibility of Aspergillus fumigatus to a novel conjugated styryl ketone.

We investigated the in-vitro and in-vivo susceptibility of Aspergillus fumigatus to the novel conjugated styryl ketone NC1175 and the results were compared with those obtained for amphotericin B and itraconazole. All 20 clinical isolates of A. fumigatus examined were susceptible to NC1175 (MIC = 5.54 +/- 2.48 mg/L; range 2.92-11.68 mg/L), and the minimum lethal concentration (MLC) was only twice the MIC, suggesting that NC1175 is fungicidal. The mean MIC values of amphotericin B (1.22 +/- 0.58 mg/L; range 0.5-4 mg/L) and itraconazole (0.37 +/- 0.11 mg/L; range 0.125-0.5 mg/L) were approximately nine- and 22-fold, respectively, lower than that of NC1175. Both amphotericin B-resistant (n = 18) and itraconazole-resistant (n = 28) isolates of A. fumigatus were as susceptible to NC1175 as amphotericin B-, and itraconazole-susceptible isolates. Kill curve experiments revealed that NC1175 at 23.35 mg/L (approximately four times the MIC) killed > or = 99% of conidia within 24 h of exposure to the drug. The in-vivo susceptibility of A. fumigatus to NC1175 was investigated using a murine pulmonary aspergillosis model. Treatment of infected mice with amphotericin B or NC1175 did not result in significant improvement of the mean survival (amphotericin B, 7.05 +/- 0.07 days; NC1175, 6.65 +/- 1.25 days) of the animals compared with that of the placebo group (7.21 +/- 1.20 days). However, semiquantitative organ culture revealed that clearance of A. fumigatus occurred in 16.6%, 50% and 66.6% of the mice treated with placebo, NC1175 and amphotericin B, respectively (P value for the control and the treated groups <0.01). These results suggest that NC1175 has in-vivo and in-vitro activity against A. fumigatus and can be used as a prototypic molecule for further development as an antifungal agent.

Amphotericin B↗

PubMed1998

Organism-dependent fungicidal activities of azoles.

We investigated the antifungal activities of itraconazole and voriconazole on Aspergillus species by time kill studies, and the results were compared with those obtained for Candida species. Exposure of Aspergillus fumigatus conidia to varying concentrations (1.25 to 10 microg/ml) of itraconazole and voriconazole resulted in cellular death; the cytocidal effect was time and concentration dependent. In contrast, no killing of Candida albicans occurred in the presence of itraconazole and voriconazole at concentrations as high as 10 microg/ml, although candidal growth was inhibited compared to the drug-free control. Amphotericin B (1.25 to 10 microg/ml), on the other hand, killed both A. fumigatus and C. albicans. Similar results were obtained for non-A. fumigatus aspergilli and non-C. albicans Candida species. These observations indicate that both itraconazole and voriconazole are cytocidal agents for Aspergillus species but not for Candida species, suggesting that azoles possess organism-dependent fungicidal activities.

Amphotericin B↗

PubMed1998

Mechanism of resistance to amikacin and kanamycin in Mycobacterium tuberculosis.

An A1400G mutation of the rrs gene was identified in Mycobacterium tuberculosis (MTB) strain ATCC 35827 and in 13 MTB clinical isolates resistant to amikacin-kanamycin (MICs, >128 microg/ml). High-level cross-resistance may result from such a mutation since MTB has a single copy of the rrs gene. Another mechanism(s) may account for high-level amikacin-kanamycin resistance in two mutants and lower levels of resistance in four clinical isolates, all lacking the A1400G mutation.

Amikacin↗