Analysis of neomycin, kanamycin, tobramycin and amikacin resistance mechanisms in gentamicin-resistant isolates of Enterobacteriaceae

Twenty-four gentamicin-resistant isolates of Enterobacteriaceae, obtained from the clinical laboratories of three health centres in Nablus, Palestine, were tested for susceptibility to neomycin, kanamycin, tobramycin and amikacin. Resistance rates were 29.2% for neomycin, 58.3% for kanamycin, 45.8% for tobramycin and 8.3% for amikacin. Fourteen (58.3%) isolates were noted to be multiresistant, i.e., resistant to gentamicin and two or more other aminoglycosides; resistance to gentamicin, kanamycin and tobramycin was the most common pattern of multiple resistance. This pattern implies the involvement of adenyltransferase ANT(")-I activity. Plasmid profiles and curing experiments suggested a plasmid localisation of gentamicin, neomycin, kanamycin and tobramycin resistance genes. However, a chromosomal location is proposed for plasmid-deficient strains. Cross-resistance in two isolates to all aminoglycosides tested suggested membrane impermeability to aminoglycosides as the mechanism of resistance.     

Spatial and temporal Mg2+ signaling in single human tracheal gland cells

Multidrug therapy is recommended for treatment of Mycobacterium avium complex (MAC) bacteremia in patients with AIDS. Azithromycin, clarithromycin, rifabutin, ciprofloxacin, ethambutol, clofazimine, and amikacin have all been suggested for use in treating MAC bacteremia, but the most active combinations of these drugs have not been identified, nor has the minimum number of drugs needed for effective therapy been determined. To address the former, the in vitro bactericidal activities of all two-, three-, and four-drug combinations of these seven agents was determined by using 10 blood-derived strains of MAC isolated from patients with AIDS. The activities of the 132 drug combinations were compared by statistical analysis of survival means (analysis of variance) and further evaluated by determining the percentage of strains considered susceptible to each combination. When susceptibility was defined as a decrease in CFU of > or = 2 log10, no two- or three-drug combination and only two four-drug combinations were active against all 10 MAC strains. When a less stringent definition was applied (> or = 1 log10 decrease in CFU), 1 two-drug combinations, 9 three-drug combinations, and 31 four-drug combinations showed activity against all 10 strains. Eighteen selected drug combinations were also tested for intracellular activity in MAC-infected J774 cells. Combinations which contained amikacin as a component were considerably less active against intracellular MAC organisms than against organisms in broth. The opposite result was obtained for the combination of clarithromycin plus clofazimine.     

In vitro activities of antimicrobial agents, alone and in combination, against Acinetobacter baumannii isolated from blood

In vitro activities of 15 antimicrobial agents against 90 strains of Acinetobacter baumannii isolated from blood cultures from hospitalized patients were determined using the agar dilution method. Imipenem, ofloxacin, and ciprofloxacin had the best antimicrobial activity with minimum inhibitory concentrations (MIC50s) of 0.25 mu g/ml and MIC90s of 0.5-1 mu g/ml. beta-lactam antibiotics other than imipenem had poor activity, with MIC50s ranging from 8 to 64 mu g/ml and MIC90s from 32 to > or = 256 mu g/ml. The checkerboard titration method was used to study the effects of combination of two antimicrobial agents. Combinations of ceftazidime, aztreonam, imipenem, or ciprofloxacin with amikacin showed either synergistic effects or partial synergistic effects for 40.9%-86.4% of 22 tested strains. The best in vitro activity was observed with the combination of imipenem and amikacin. No antagonistic effects were observed with the combination of imipenem and amikacin. Synergistic effects were confirmed by time-kill curve studies. In conclusion, imipenem, ofloxacin, and ciprofloxacin were the three most active agents against human blood isolates of A. baumannii. The combination of a beta-lactam or ciprofloxacin with amikacin was synergistic for some of the isolates.     

In vitro antibacterial activity of cefoperazone-sulbactam

This study was conducted to evaluate the antibacterial activity of CPZ-SBT in 1,146 clinical isolates and compared with that of CPZ and other antimicrobial agents. CPZ-SBT has much better antibacterial activity than CPZ against B-lactamase producing organisms. Of the 834 gram negative organisms tested, 165 were CPZ resistant, but 94 (57.0%) of them were still susceptible to CPZ-SBT, CPZ-SBT broadens the antibacterial spectrum of CPZ, it has good activity against Acinetobacter spp and B fragilis. Compared with other antimicrobial agents tested, CPZ-SBT is as active as ceftazidime, amikacin and ciprofloxacin against Enterobacteriaceae, P aeruginosa and Acinetobacter spp, but slightly less active than imipenem. It is as active as imipenem, timentin and metronidazole against B fragilis and other anaerobes. The results show that CPZ-SBT is a new member of the broad spectrum antimicrobial agents. It may become a promising agent for the treatment of severe infections caused by cefoperazone-resistant Gram negative bacilli including P aeruginosa.     

A six-year retrospective analysis of shoulder dystocia and delivery of the shoulders

Gentamicin (GM) has been shown to reversibly reduce the ability of contralateral noise to suppress ipsilateral cochlear activity, in a dose-dependent manner. However, during chronic administration of lower doses (60 mg/kg) the involvement of medial efferents could not be demonstrated. The purposes of the present study were to determine whether other aminoglycosides would display the same acute effects as GM and whether there was any correlation between their specificity and degree of cochlear and vestibular toxicity and their potency of blockade of the medial efferent system. Thus, we observed changes in ipsilateral ensemble background activity (EBA) of the VIIIth nerve without and with contralateral low level (55 dB SPL) broadband noise stimulation, in awake guinea pigs (GPs), before and after one single high-dose intramuscular injection of different aminoglycoside antibiotics (AAs) (gentamicin, amikacin, neomycin, netilmicin, streptomycin, tobramycin). For comparison, the effects of strychnine, a known antagonist of the efferent transmission and of cisplatin, an antineoplastic agent with cochleotoxic properties were also studied. Netilmicin displayed blocking properties similar to GM, although less pronounced, while amikacin and neomycin had no effect on medial efferent function. With tobramycin and streptomycin a decrease in suppression was usually associated with a reduction of the EBA measured without acoustic stimulation. However, with cisplatin, suppression was still effective when EBA was severely decreased. We could not observe specific effects of strychnine on medial efferent function. In conclusion, no correlation was found between specificity and degree of AA ototoxicity and their action on the medial efferent system.     

Neomycin inhibits angiogenin-induced angiogenesis

A class of angiogenesis inhibitor has emerged from our mechanistic study of the action of angiogenin, a potent angiogenic factor. Neomycin, an aminoglycoside antibiotic, inhibits nuclear translocation of human angiogenin in human endothelial cells, an essential step for angiogenin-induced angiogenesis. The phospholipase C-inhibiting activity of neomycin appears to be involved, because U-73122, another phospholipase C inhibitor, has a similar effect. In contrast, genistein, oxophenylarsine, and staurosporine, inhibitors of tyrosine kinase, phosphotyrosine phosphatase, and protein kinase C, respectively, do not inhibit nuclear translocation of angiogenin. Neomycin inhibits angiogenin-induced proliferation of human endothelial cells in a dose-dependent manner. At 50 microM, neomycin abolishes angiogenin-induced proliferation but does not affect the basal level of proliferation and cell viability. Other aminoglycoside antibiotics, including gentamicin, streptomycin, kanamycin, amikacin, and paromomycin, have no effect on angiogenin-induced cell proliferation. Most importantly, neomycin completely inhibits angiogenin-induced angiogenesis in the chicken chorioallantoic membrane at a dose as low as 20 ng per egg. These results suggest that neomycin and its analogs are a class of agents that may be developed for anti-angiogenin therapy.     

The antimicrobial susceptibility of Mycobacterium chelonae isolated from corneal ulcer

PURPOSE: To determine the in vitro susceptibility of Mycobacterium chelonae isolates from corneal ulcers to various traditional and newly-developed antimicrobial agents, alone or in combination. METHODS: Fifteen strains of M. chelonae isolated from corneal ulcers were collected at the National Taiwan University Hospital from 1989 to 1993. Susceptibility to antimicrobial agents was tested by the broth microdilution method to determine the minimum inhibitory concentration (MIC). The antimicrobial effects of combinations of antimicrobial agents were assessed by the checkerboard titration method to determine the fractional inhibitory concentration (FIC) index. RESULTS: The MIC results showed that traditional antituberculous drugs had poor activity against M. chelonae. In the aminoglycoside group, tobramycin and amikacin had better activity than gentamicin. Among macrolides, clarithromycin was especially effective, with an MIC ranging from 0.125 to 1 microgram/ml. Among various beta-lactam antibiotics, imipenem was the only one to demonstrate good anti-mycobacterial activity. Of the quinolone group, ciprofloxacin was the most effective, with an MIC ranging from 0.5 to 16 micrograms/ml. Combination of an aminoglycoside with imipenem, ciprofloxacin or clarithromycin all showed antagonistic effect. CONCLUSIONS: The results suggested that amikacin, clarithromyicn, imipenem and ciprofloxacin had good in vitro antimicrobial activity against M. chelonae. However, no synergistic effect could be demonstrated for combinations of an aminoglycoside with other effective drugs.     

Characterization of natural isolate Lactobacillus acidophilus BGRA43 useful for acidophilus milk production

The adherence of P. aeruginosa to collagen membrane, sponge, and to a new anti-infective COLL dressing and the susceptibility of the organisms attached to the biomaterials to amikacin were investigated in vitro. After 17 h of attachment, the bacteria demonstrated an increased resistance to amikacin compared with their free-floating counterparts. Amikacin, even at a concentration exceeding 150 times the minimal bactericidal concentration (MBC) for the strain tested, did not eradicate the attached bacteria from the surface of collagen membrane. However, when the drug at a high concentration (over 16 times the minimal inhibitory concentration, MIC) was present in the incubation medium before it had been inoculated with P. aeruginosa, a reduction of 2 log10 units in the organisms adherent to the surface of collagen membrane was observed. We conclude that slow release of the antibiotic from the COLL dressing could control the bacterial colonization on the surface. In fact, the released amikacin at the final concentration of 32 times the MBC reduced the number of adherent bacteria by 6 log10 units. In contrast, ciprofloxacin at the same final bactericidal concentration completely eradicated the bacteria from the surface of COLL dressing. However, as ciprofloxacin is not recommended for use as a topical antimicrobial agent, a further search is needed to find an agent with a similar anticolonization activity.     

A single 16S ribosomal RNA substitution is responsible for resistance to amikacin and other 2-deoxystreptamine aminoglycosides in Mycobacterium abscessus and Mycobacterium chelonae

Twenty-six clinical isolates of Mycobacterium abscessus resistant to amikacin were identified. Most isolates were from patients with posttympanostomy tube placement otitis media or patients with cystic fibrosis who had received aminoglycoside therapy. Isolates were highly resistant (MICs > 1024 microg/mL) to amikacin, kanamycin, gentamicin, tobramycin, and neomycin (all 2-deoxystreptamine aminoglycosides) but not to streptomycin. Sequencing of their 16S ribosomal (r) RNA revealed that 16 (94%) of 17 had an A-->G mutation at position 1408. In vitro-selected amikacin-resistant mutants of M. abscessus and Mycobacterium chelonae had the same resistance phenotype, and 15 mutants all had the same A-->G substitution at position 1408. Introducing an rRNA operon from Mycobacterium smegmatis with a mutated A-->G at this position into a single functional allelic rRNA mutant of M. smegmatis produced the same aminoglycoside resistance phenotype. These studies demonstrate this 16S rRNA mutation is responsible for amikacin resistance in M. abscessus, which has only one copy of the rRNA operon.     

Selection and characterization of strains of Staphylococcus aureus displaying unusual resistance to aminoglycosides

Susceptibility tests with aminoglycosides against Staphylococcus aureus have revealed discrepancies between the minimal inhibitory concentrations and the minimal bactericidal concentrations. To further evaluate these discrepancies, kill curves were performed against a susceptible strain of S. aureus with five different aminoglycosides (amikacin, kanamycin, tobramycin, gentamicin, sisomicin) at concentrations up to 16-fold above the minimal inhibitory concentration. Results revealed the presence of small subpopulations of cells capable of growth within 24 h in concentrations of aminoglycoside up to eightfold above the minimal inhibitory concentration for the parent strain. These subpopulations occurred at a frequency of >/=10(-7) parent cells, were not physiologically different from the susceptible parent strains, and were present in approximately one-half of 30 strains of S. aureus tested. The resistance of these subpopulations was approximately eightfold higher than that of the parent for all five aminoglycosides and was independent of concentration or type of aminoglycoside used to select them. This resistance was not due to extracellular degradation of drug and was stable over eight transfers in drug-free medium, except when selected by gentamicin or sisomicin.     

Antibiotic susceptibility of Mycoplasma fermentans strains from various sources and the development of resistance to aminoglycosides in vitro

Mycoplasma fermentans strains reputedly from human infections or tissue culture cells were much more susceptible to azithromycin than to clarithromycin or erythromycin. Lincomycin, clindamycin and several tetracyclines also exhibited good mycoplasmastatic activity but mycoplasmacidal concentrations were substantially greater than the MICs. Ciprofloxacin was the most active of three fluoroquinolones tested and was mycoplasmacidal at concentrations close to the MIC. Tiamulin and mupirocin were also very active. Synergy with specific M. fermentans antiserum plus guinea-pig complement was not observed with any class of antibiotic although the number of viable mycoplasmas was markedly reduced by the combined immunological components. Marked differences in susceptibility to various aminoglycosides were observed. Human strains isolated in cell-free media up to 1967 were aminoglycoside susceptible (MIC range 0.5-25 mg/L) but recent human isolates and strains isolated from tissue culture cells often showed either single or multiple aminoglycoside resistance (MIC > 500 mg/L). Two aminoglycoside-susceptible strains developed resistance to streptomycin or neomycin (> 500 mg/L) within five passages in broth containing streptomycin or neomycin, respectively. Resistance to tobramycin, kanamycin or gentamicin emerged after seven, eight and 14 cycles of exposure to the respective antibiotic. Streptomycin resistance was associated with a five-fold increase in resistance to tobramycin. Neomycin-, kanamycin-, gentamicin- and tobramycin-resistant variants showed mutual cross-resistance but remained susceptible to streptomycin. Induced resistance persisted for at least 17 passages in aminoglycoside-free broth. The use of aminoglycosides in human medicine and the frequent inclusion of some of these drugs in tissue cell cultures to combat bacterial and mycoplasmal contamination might account for the aminoglycoside resistance of recent M. fermentans isolates.     

Should vancomycin be used empirically in febrile patients with prolonged and profound neutropenia? Results of a randomized trial

OBJECTIVES: We conducted a randomized trial with ceftazidine alone or associated with amikacin or vancomycin to investigate the efficacy of the daily 3 g dosage of ceftazidime and the efficacy of monotherapy with ceftazidime and to determine if vancomycin should be added empirically. METHODS: Patient inclusion criteria were: age over 10 years, therapeutically-induced neutropenia and fever for at least three hours above 38.5 degrees C in absence of a clear non-infectious aetiology. Patients were randomized into three groups: group C, ceftazidime alone 3 g/day; group CA, ceftazidime 3 g/day plus amikacin 15 mg/kg/day; or group C, ceftazidime 3 g/day plus vancomycin 1.5 g/day. RESULTS: Results from one hundred and two episodes of fever were analyzed. The underlying diseases were haematological malignancies (89 patients) and solid tumours (13 patients). The median duration of neutropenia (< 0.5 x 10(9) PMN/L) was 18 days and the minimum duration of 7 days. The main criterion for the analysis of efficacy was the onset of a major infectious event, i.e. death related to documented or suspected infection and any infectious event considered life-threatening or hindering future treatment of the underlying disease. Eight (22%) patients in group C developed major infectious events compared with four (13%) in group CA and none in group CV (p < 0.01). Major infectious events were mainly due to Gram-positive organisms, particularly Streptococcus species. CONCLUSION: We conclude that: 1) ceftazidime alone and in association with amikacin is effective in preventing Gram-negative major infectious events; and 2) vancomycin should not be added only when a Gram-positive infection is documented, but used empirically.     

In vitro activity of netilmicin compared with gentamicin, tobramycin, amikacin, and kanamycin

The in vitro activity of netilmicin was compared with that of gentamicin, tobramycin, amikacin, and kanamycin against 636 strains of bacteria recently isolated from clinical sources. Gentamicin was the most active antibiotic, but netilmicin and tobramycin closely paralleled it. Netilmicin was generally four-to eightfold less active than gentamicin against Serratia and group A streptococci, and was twofold less active against Pseudomonas aeruginosa. When effects of inoculum size and concentration of divalent cations in the media were evaluated, netilmicin was shown to be similar to gentamicin in vitro. Minimum inhibitory concentrations for P. aeruginosa were increased as much as 18-fold when the Mg(2+) and Ca(2+) concentrations were increased to physiological levels in Mueller-Hinton broth.     

Effect of gentamicin on early mortality and later performance of broiler and Leghorn chickens

Field and floor-pen trials demonstrated that subcutaneous injection of 0.2 mg gentamicin at one day old reduced bacteria-caused deaths in White Leghorn and broiler-type chicks. Growth, feed efficiency, and condemnation data from broiler trials suggested an advantage for treated chickens over unmedicated controls. Ninety-nine percent of clinical isolates were susceptible to gentamicin (10 mug) when tested by the modified Kirby-Bauer method. In vitro susceptibilities of these isolates to neomycin, nitrofurazone, chloramphenicol, and kanamycin varied from 90 to 94%. About half of the isolates were susceptible to dihydrostreptomycin or tetracycline in vitro, while less than 10% were susceptible to penicillin or clindamycin. In vitro tests to determine the lowest concentration of antibiotics required to inhibit the growth of 31 bacterial isolates demonstrated that less gentamicin is required than neomycin, spectinomycin, or oxytetracycline.     

Detection of aminoglycoside-penicillin synergy against Enterococcus faecium using high-content aminoglycoside disks

Thirty-seven Enterococcus faecium strains were screened for high-level aminoglycoside resistance with an agar diffusion test using high-content aminoglycoside disks (300 micrograms of streptomycin and 120 micrograms of gentamicin, tobramycin, kanamycin or amikacin). The inhibition zones obtained were correlated with results of time-kill penicillin-aminoglycoside synergy studies. An 11 mm breakpoint differentiated strains susceptible or resistant to the synergy of streptomycin plus penicillin. Irrespective of the inhibition zones obtained with tobramycin and kanamycin disks, Enterococcus faecium strains never showed synergy with penicillin in combination with these aminoglycosides. Penicillin-amikacin synergy cannot be predicted by the amikacin disks. Nevertheless, even though kanamycin disks do not predict penicillin-kanamycin synergy, they can be used to predict penicillin-amikacin synergy. In summary, high-content streptomycin, gentamicin and kanamycin disks can be used to predict the susceptibility of Enterococcus faecium strains to the synergistic combination of penicillin plus one of the aminoglycosides (streptomycin, gentamicin or amikacin, respectively).     

Resistance to gentamicin, tobramycin and amikacin among clinical isolates of bacteria

Susceptibility to the administration of gentamicin, tobramycin and amikacin was determined for all isolates of aerobic and facultative gram-negative bacilli submitted for testing to the clinical bacteriology laboratory of the Massachusetts General Hospital between July 1, 1974, and June 30, 1976. In this 24-month period more than 46,000 isolates of bacteria were tested by the single-disc diffusion (Bauer-Kirby) method. Resistance to one or more of the aforementioned aminoglycosidic aminocyclitol antibiotics was found among 4,114 stains. Correlation with quantitative susceptibility test methods revealed that disc-diffusion methods using 10 microng discs accurately predicted resistance to gentamicin and tobramycin, but overestimated the prevalence of resistance to amikacin by 20 to 60%. Most of the gentamicin-resistant Enterobacteriaceae in this study were also cross-resistant to tobramycin but were susceptible to amikacin. Many gentamicin-resistant strains of Ps. aeruginosa were susceptible to both tobramycin and amikacin. Resistance to amikacin tended to be of relatively low magnitude (most had minimal inhibitory concentrations (MIC's) between 31 and 125 microng/ml), but organisms which were resistant to the administration of amikacin were usually resistant to the other two aminoglycosidic antibiotics as well.     

Meropenem versus ceftazidime plus amikacin in the treatment of febrile episodes in neutropenic patients: a randomized study

BACKGROUND AND OBJECTIVE: Meropenem is the first of a new class of carbapenems which may be administered without cilastatin. This study was performed to assess the clinical efficacy and tolerability of meropenem monotherapy (1 g/8 h) compared with the standard combination of ceftazidime (2 g/8 h) plus amikacin (15 mg/kg/day) for the empirical treatment of infective febrile episodes in neutropenic cancer patients. METHODS: This was a three-center, randomized, non-blind parallel group trial. The primary objective was to compare the clinical efficacy of meropenem monotherapy with that of ceftazidime plus amikacin in the empirical treatment of febrile infective episodes in neutropenic patients. This was evaluated by the number of patients surviving on unmodified therapy at 72 h (primary end point) and by the clinical response at the end of therapy (secondary end point). RESULTS: A total of 93 febrile episodes (46 meropenem, 47 ceftazidime/amikacin) were evaluable. Bone marrow transplant patients accounted for 49.5% of all cases. There was a high incidence of Gram-positive infections but no pseudomonal infections. Microbiologically documented infections, clinically documented infections and unexplained fever accounted for 45%, 10% and 45% of episodes, respectively. There was a similar proportion of patients in the meropenem and ceftazidime/amikacin groups on unmodified empiric therapy at 72 h (80.4% vs 76.6%, p = 0.65,) and cured at the end of therapy (37% vs 36.2%, p = 0.9). No significant difference in tolerability was observed between the groups. Meropenem was well tolerated; of note, there were no cases of nausea/vomiting or seizure related to its use. INTERPRETATION AND CONCLUSIONS: Meropenem monotherapy was well tolerated and produced response rates similar to those obtained with ceftazidime/amikacin. The low overall success rates with both treatments concur with those of other recent studies and are probably due to a combination of several factors, including the adoption of strict assessment criteria.     

Neomycin B inhibits splicing of the td intron indirectly by interfering with translation and enhances missplicing in vivo

The aminoglycoside antibiotic neomycin B inhibits translation in prokaryotes and interferes with RNA-protein interactions in HIV both in vivo and in vitro. Hitherto, inhibition of ribozyme catalysis has only been observed in vitro. We therefore monitored the activity of neomycin B and several other aminoglycoside antibiotics on splicing of the T4 phage thymidylate synthase (td) intron in vivo. All antibiotics tested inhibited splicing, even chloramphenicol, which does not inhibit splicing in vitro. Splicing of the td intron in vivo requires translation for proper folding of the pre-mRNA. In the absence of translation, two interactions between sequences in the upstream exon and the 5' and 3' splice sites trap the pre-mRNA in splicing-incompetent conformations. Their disruption by mutations rendered splicing less dependent on translation and also less sensitive to neomycin B. Intron splicing was affected by neither neomycin B nor gentamicin in Escherichia coli strains carrying antibiotic-resistance genes that modify the ribosomal RNA. Taken together, this demonstrates that in vivo splicing of td intron is not directly inhibited by aminoglycosides, but rather indirectly by their interference with translation. This was further confirmed by assaying splicing of the Tetrahymena group I intron, which is inserted in the E. coli 23 S rRNA and, thus, not translated. Furthermore, neomycin B, paromomycin, and streptomycin enhanced missplicing in antibiotic-sensitive strains. Missplicing is caused by an alternative structural element containing a cryptic 5' splice site, which serves as a substrate for the ribozyme. Our results demonstrate that aminoglycoside antibiotics display different effects on ribozymes in vivo and in vitro.     

Neomycin: microbiological assay or liquid chromatography?

In a multicentre study involving six laboratories, a microbiological assay was performed on three neomycin samples containing respectively, 0.12, 2.1 and 11% (m/m) of neomycin C, as well on a pure neomycin C sample. The potency was determined according to the European Pharmacopoeia method but using a neomycin B base standard. The relative standard deviations between laboratories (RSD) on the potencies varied from 4.8 to 50%, depending on the sample examined. The RSD increased with the neomycin C content of the samples and the highest RSD values were observed for the pure neomycin C sample. The activity of neomycin C relative to neomycin B was found to be 62% by diffusion (RSD:41%) and 56% by turbidimetry (RSD: 50%). This confirmed that the presence of neomycin C in a neomycin sample influences the reproducibility of the microbiological assay. T estimate the influence of this effect on official standard, their composition was verified by liquid chromatography. The neomycin C base content of the standards varied between 0.4 and 5.8% (m/m). Based on the results obtained and on formerly published reports discussing problems encountered with microbiological assay of neomycin, it is proposed to introduce liquid chromatography in official monographs to replace microbiological assay.     

Antifungal pharmacodynamic characteristics of fluconazole and amphotericin B tested against Candida albicans

Time-kill curves were determined for three isolates of Candida albicans tested against fluconazole and amphotericin B at multiples of the MIC. Fluconazole produced fungistatic activity, with concentration-related growth effects observed over a narrow range of concentrations. Amphotericin B exhibited fungicidal activity, with enhancement of activity over a broader range of concentrations.