Quinolone effects in the SOS chromotest and in the synthesis of biomacromolecules

The genotoxicity of quinolone antibiotics (ciprofloxacin, enoxacin, nalidixic acid, norfloxacin, ofloxacin, pefloxacin) was studied on the selected mutantE. coli strain PQ37 (SOS chromotest). The genotoxicity was expressed by SOS-inducing potential (SOSIP) values. The highest SOSIP values were found with ciprofloxacin (SOSIP=1967 δIF/nmol), the lowest value was observed with nalidixic acid (SOSIP=0.3 ΔIF/nmol). Similar results were also found with the biosynthesis of nucleic acids, as indicated by incorporation of¹⁴C-adenine into TCA-insoluble fractions ofS. typhimurium cells (ciprofloxacin IC₅₀=0.39, nalidixic acid IC₅₀=400). DNA-damaging effects were tested in the absence of an exogenous metabolizing system.     

Ciprofloxacin-Induced Antibacterial Activity is Reversed by Vitamin E and Vitamin C

In the present study, we investigated the possible involvement of oxidative stress in ciprofloxacin-induced cytotoxicity against several reference bacteria including Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 29213, and clinical isolate of methicillin-resistant Staphylococcus aureus (MRSA). Oxidative stress was assessed by measurement of hydrogen peroxide generation using a FACScan flow cytometer. The antibacterial activity of ciprofloxacin was assessed using the disk diffusion method and by measuring the minimum inhibitory concentration (MIC). Ciprofloxacin induced a dose-dependent antibacterial activity against all bacteria where the highest tested concentration was 100 ug/ml. Results revealed that E. coli cells were highly sensitive to ciprofloxacin (MIC = 0.21 μg/mL ± 0.087), P. aeruginosa and S. aureus cells were intermediately sensitive (MIC = 5.40 μg/mL ± 0.14; MIC = 3.42 μg/mL ± 0.377, respectively), and MRSA cells were highly resistant (MIC = 16.76 μg/mL ± 2.1). Pretreatment of E. coli cells with either vitamin E or vitamin C has significantly protected cells against ciprofloxacin-induced cytotoxicity. These results indicate the possible antagonistic properties for vitamins C or E when they are used concurrently with ciprofloxacin.     

Determination of the Efflux Pump-Mediated Resistance Prevalence in Pseudomonas aeruginosa, Using an Efflux Pump Inhibitor

In Gram negative bacteria, fluoroquinolone resistance is acquired by target mutations in topoisomerase genes or by reducing the permeation of drugs due to the increase in expression of endogenous multidrug efflux pumps that expel structurally unrelated antimicrobial agents. An ongoing challenge is searching for new inhibitory substances in order to block efflux pumps and restore the antibiotic drugs susceptibility. In this research, we sought to investigate the interplay between ciprofloxacin and an efflux pump inhibitor (EPI), phenyl alanine arginyl β-naphtylamide (PAβN), to determine the prevalence of efflux pump overexpression in clinical isolates of Pseudomonas aeruginosa. Ciprofloxacin was tested at different concentrations (256–0.25 μg/ml) with a fixed concentration of PAβN (50 μg/ml). The isolates susceptibility profiles were analyzed by disc diffusion and agar dilution methods using 10 antibiotic discs and 4 powders. It was found that in the presence of PAβN, resistance to ciprofloxacin was inhibited obviously and MIC values were decreased. The comparison between subgroups of P. aeruginosa isolates with different resistance profiles indicates that efflux pump overexpression (EPO) is present in 35% of ciprofloxacin resistant isolates with no cross resistance and in variable frequencies among isolates showing cross resistance to other tested antibiotics: gentamicin (31%), ceftazidime (29%), and imipenem (18%). Altogether, these results imply that PAβN maybe effective to restore the fluoroquinolone drugs susceptibility in clinical treatment procedures. Results also show that increased use of a fluoroquinolone drug such as ciprofloxacin can affect the susceptibility of P. aeruginosa to other different antipseudomonal agents.     

Sensitivity of Pseudomonas mallei to fluoroquinolones and their efficacy in experimental glanders]

Thirteen strains of P. mallei were found to be highly sensitive to ciprofloxacin and ofloxacin and resistant to norfloxacin. Ciprofloxacin and ofloxacin showed a high efficacy on models of malleus in guinea pigs and hamsters. The animals were infected with various strains of P. mallei. In the in vitro experiments, ciprofloxacin proved to be the most active and efficient. Norfloxacin appeared to be inefficient.     

In vitro antifungal activities of voriconazole and reference agents as determined by NCCLS methods: Review of the literature

Voriconazole (Vfend™) is a new triazole that currently is undergoing phase III clinical trials. This review summarizes the published data obtained by NCCLS methods on the in vitro antifungal activity of voriconazole in comparison to itraconazole, amphotericin B, fluconazole, ketoconazole and flucytosine. Voriconazole had fungistatic activity against most yeasts and yeastlike species (minimum inhibitory concentrations [MICs] <2 μg/ml) that was similar or superior to those of fluconazole, amphotericin B, and itraconazole. Against Candida glabrata and C. krusei, voriconazole MIC ranges were 0.03 to 8 and 0.01 to >4 μg/ml, respectively. For four of the six Aspergillus spp. evaluated, voriconazole MICs (< 0.03 to 2 μg/ml) were lower than amphotericin B (0.25 to 4 μg/ml) and similar to itraconazole MICs. Voriconazole fungistatic activity against Fusarium spp. has been variable. Against F. oxysporum and solani, most studies showed MICs ranging from 0.25 to 8 μg/ml. Voriconazole had excellent fungistatic activity against five of the six species of dimorphic fungi evaluated (MIC₉₀s < 1.0 μg/ml). The exception was Sporothrix schenckii (MIC₉₀s and geometric mean MICs ≥ 8 μg/ml). Only amphotericin B had good fungistatic activity against the Zygomycetes species (voriconazole MICs ranged from 2 to >32 μg/ml). Voriconazole showed excellent in vitro activity (MICs < 0.03 to 1.0 μg/ml) against most of the 50 species of dematiaceous fungi tested, but the activity of all the agents was poor against most isolates of Scedosporium prolificans and Phaeoacremonium parasiticum (Phialophora parasitica). Voriconazole had fungicidal activity against most Aspergillus spp., B. dermatitidis, and some dematiaceous fungi. In vitro/in vivo correlations should aid in the interpretation of these results. This revised version was published online in June 2006 with corrections to the Cover Date.     

Synthesis and antituberculosis activity of derivatives of <Emphasis Type="Italic">Stevia rebaudiana</Emphasis> glycoside steviolbioside and diterpenoid isosteviol containing hydrazone,hydrazide, and pyridinoyl moieties

Conjugates of the antituberculosis drug isoniazid (isonicotinyl hydrazine) and isomeric hydrazides of nicotinic and α-picolinic acid with glycoside steviolbioside from the Stevia rebaudiana plant and the product of its acid hydrolysis, diterpenoid isosteviol, were synthesized. In addition, isosteviol hydrazide and hydrazone derivatives as well as conjugates containing two isosteviol moieties joined by a dihydrazide linker were obtained. The parental compounds and their synthetic derivatives were found to inhibit the in vitro growth of Mycobacterium tuberculosis (H₃₇R_V). The measured minimal concentrations of stevio-side and steviolbioside, at which the growth of M. tuberculosis was inhibited by 100% (MIC), were 7.5 and 3.8 μg/ml, respectively. MIC values for steviolbioside and isosteviol conjugates with hydrazides of pyridine carbonic acid were within the ranges of 5–10 and 10–20 μg/ml, respectively. The maximal inhibitory effect against M. tuberculosis was shown by the isosteviol conjugates with adipic acid dihydrazide (MIC 1.7 and 3.1 μg/ml). Antituberculosis activities of the tested compounds were higher than the activity of antituberculosis drug Pyrizanamide (MIC 20 μg/ml) but lower than that of antituberculosis drug isoniazid (MIC 0.02–0.04 μg/ml).     

The Role of Fluoroquinolones in the Promotion of Alginate Synthesis and Antibiotic Resistance in Pseudomonas aeruginosa

Treatment of nonmucoid Pseudomonas aeruginosa with gyrase inhibitors such as ciprofloxacin, norfloxacin, and ofloxacin, which target the A subunit of topoisomerase II, resulted in 100% conversion to the mucoid phenotype. However, antibiotics that partially inhibited growth and macromolecular synthesis (DNA, RNA, protein, or peptidoglycan) of nonmucoid isolates in a gluconate-limited chemostat culture system did not promote conversion to mucoid subpopulations. An increase in resistance was observed in populations that expressed the mucoid phenotype. Both mucoid conversion and antibiotic resistance were completely reversible when ciprofloxacin pressure was withdrawn, but only partially reversible by the removal of norfloxacin and ofloxacin. Thus, these experiments indicate that in the presence of some fluoroquinolones, a conditional response resulting in mucoid conversion and antibiotic resistance may occur. Received: 28 January 1997 / Accepted: 12 February 1997     

Fluconazole-, Amphotericin-B-, Caspofungin-, and Anidulafungin-Resistant <Emphasis Type="Italic">Candida ciferrii</Emphasis>: An Unknown Cause of Systemic Mycosis in a Child

Candida ciferrii, which is known as an agent of superficial yeast infection and onychomycosis, has rarely been isolated as an agent of candidemia. Limited reports have suggested different patterns of antifungal sensitivity. We report a rare candidemia case caused by c.ciferrii in an 8-year-old child in which isolated candida species were resistant to amphotericin-B (MIC > 1 μg/ml), fluconazole, (MIC ≥ 64 μg/ml), caspofungin (MIC ≥ 32 μg/ml), and anidulafungin (MIC ≥ 32 μg/ml) but sensitive to voriconazole (MIC ≤ 0.12 μg/ml). As far as we aware, this was the first recorded C. ciferrii candidemia case in children.     

In Vitro Activities of Fourteen Antimicrobial Agents Against Drug Susceptible and Resistant Clinical Isolates of Mycobacterium tuberculosis and Comparative Intracellular Activities Against the Virulent H37Rv Strain in Human Macrophages

Minimal inhibitory concentrations (MICs) of 14 first and second-line antituberculous drugs against drug-susceptible and drug-resistant clinical isolates of Mycobacterium tuberculosis (including the multiple drug-resistant or MDR-TB isolates), as well as the type strain H37Rv, were determined radiometrically by the Bactec 460-TB methodols. MICs (μg/ml) of all the fourteen drugs were within an extremely narrow range in case of susceptible strains; isoniazid (0.02–0.04), rifampin (0.2–0.4), ethambutol and streptomycin (0.5–2.0), ethionamide (0.25–0.5), D-cycloserine (25–75), capreomycin (1–2), kanamycin (2–4), amikacin (0.5–1.0), clofazimine (0.1–0.4), ofloxacin (0.5–1.0), ciprofloxacin (0.25–1.0), and sparfloxacin (0.1–0.4). The activity of second-line drugs remained unaltered against MDR-TB isolates resistant to routine first-line drugs. With peak serum level concentrations (Cmax), the intracellular killing of the virulent H37Rv strain was studied in detail in cultured human macrophages. Based on an decreasing order of bactericidal activity, our results showed the following spectrum of intracellular drug action: among the first-line drugs, rifampin > ethionamide = isoniazid > ethambutol > streptomycin > D-cycloserine; among second-line drugs, clofazimine = amikacin > kanamycin = capreomycin; among fluoroquinolones, sparfloxacin > ofloxacin > ciprofloxacin. On the other hand, contrary to atypical mycobacteria, the macrolide drug clarithromycin was inactive against both extracellular and intracellular M. tuberculosis. Received: 23 January 1996 / Accepted: 5 April 1996     

Resistance to Antimicrobial Agents in Lactobacilli Isolated from Caper Fermentations

A collection of lactobacilli comprising species of Lactobacillus plantarum (43 isolates), Lactobacillus brevis (9 isolates) and Lactobacillus fermentum (6 isolates) obtained from spontaneous fermentations of capers (the fruits of Capparis spinosa) were investigated for resistance to antimicrobial agents. All isolates were resistant to vancomycin and teicoplanin (MIC > 16 μg/ml). Resistance to ciprofloxacin (MIC > 2 μg/ml) was detected in all isolates of L. brevis and L. fermentum as well as in most isolates of L. plantarum, whilst resistance to levofloxacin showed a much lower incidence. Among L. plantarum and L. brevis isolates, low levels of resistance to tetracycline and/or nitrofurantoin were detected. Higher resistance levels were also detected in some isolates. Resistance to penicillin and rifampicin were also detected among L. plantarum isolates. All isolates were sensitive to ampicillin, erythromycin, chloramphenicol, gentamicin, streptomycin, and quinupristin/dalfopristin.     

Antibiotic Susceptibility of Helicobacter pylori Clinical Isolates: Comparative Evaluation of Disk-Diffusion and E-Test Methods

Antimicrobial susceptibility of 25 Helicobacter pylori strains isolated from patients with acid peptic diseases were tested for in vitro sensitivity to commonly used antibiotics using disk-diffusion and E-test, methods. All strains tested were susceptible to tetracycline by E-test, with the minimum inhibitory concentration (MIC) values being <0.125 μg/ml for all strains except for 6 (<0.023 μg/ml). However 1 strain was resistant by disk-diffusion method. One strain was resistant to clarithromycin both by disk diffusion and E-test (MIC <48 μg/ml), and 1 strain was resistant only by disk diffusion. Only one strain was resistant to amoxicillin by disk diffusion and E-test (MIC >256 μg/ml). For ciprofloxacin, three strains were resistant by disk diffusion and two by E-test (MIC <32 μg/ml). Sixteen strains were resistant to metronidazole by disk diffusion and E-test (MIC ≥ 8 μg/ml), and 1 was resistant only by E-test (MIC <48 μg/ml). Overall, 64% of the strains were resistant to metronidazole. The MIC for metronidazole was also tested by agar-dilution method, and metronidazole resistant strains had an, MIC >8 μg/ml. The disk-diffusion method showed excellent correlation with E-test results; there was 100% agreement for amoxicillin a other antibiotics showed 90% to 95% accuracy. Disk diffusion is cheaper than E-test (approximately 2.6 cents vs. US$2.60), is easy to perform, and is a reliable method for testing H. pylori susceptibility to antimicrobial agents in the clinical microbiology laboratory.     

Camptothecin-resistant fungal endophytes of <Emphasis Type="Italic">Camptotheca acuminata</Emphasis>

Concentrations of the DNA topoisomerase I inhibitor camptothecin were determined in different tissues of Camptotheca acuminata (Nyssaceae). The data were dependent on tissue type and developmental stage. Despite the presence of the toxic compound camptothecin, nine endophytic fungi were isolated from healthy C. acuminata plants and were tested for their camptothecin sensitivity. Two isolates showed almost no inhibition at a camptothecin concentration of 10 μg/ml. Even at a concentration of 100 μg/ml the inhibition was moderate.     

Interaction of benzo[c]phenanthridine and protoberberine alkaloids with animal and yeast cells

We compared the effects of four quaternary benzo[c]phenanthridine alkaloids – chelerythrine, chelilutine, sanguinarine, and sanguilutine – and two quaternary protoberberine alkaloids – berberine and coptisine – on the human cell line HeLa (cervix carcinoma cells) and the yeastsSaccharomyces cerevisiae andSchizosaccharomyces japonicus var. versatilis. The ability of alkaloids to display primary fluorescence, allowed us to record their dynamics and localization in cells. Cytotoxic, anti-microtubular, and anti-actin effects in living cells were studied. In the yeasts, neither microtubules nor cell growth was seriously affected even at the alkaloid concentration of 100 μg/ml. The HeLa cells, however, responded to the toxic effect of alkaloids at concentrations ranging from 1 to 50 μg/ml. IC₅₀ values for individual alkaloids were: sanguinarine IC₅₀ = 0.8 μg/ml, sanguilutine IC₅₀ = 8.3 μg/ml, chelerythrine IC₅₀ = 6.2 μg/ml, chelilutine IC₅₀ = 5.2 μg/ml, coptisine IC₅₀ = 2.6 μg/ml and berberine IC₅₀ >10.0 μg/ml. In living cells, sanguinarine produced a decrease in microtubule numbers, particularly at the cell periphery, at a concentration of 0.1 μg/ml. The other alkaloids showed a similar effect but at higher concentrations (5–50 μg/ml). The strongest effects of sanguinarine were explained as a consequence of its easy penetration through the cell membrane owing to nonpolar pseudobase formation and to a high degree of molecular planarity. This revised version was published online in July 2006 with corrections to the Cover Date.     

A novel bacterial pathogen (Enterobacter sp.) isolated from the leaf roller, Caloptilia theivora of tea of Darjeeling foothills

Enterobacter sp. was isolated from the diseased and dead caterpillars of the tea leaf roller (Caloptilia theivora) from the Darjeeling foothill region. When the vegetative form of the bacterium was applied via food, mortality of C. theivora showed an LC₅₀ value at 363.1 μg/ml (bacterial wt./vol. of water) with fiducial limits 363.25 and 362.94 μg/ml respectively. The LT₅₀ values for C. theivora were 6 days for 100 μg/ml, 5.96 days for 300 μg/ml, 5.81 days for 500 μg/ml, 4.96 days for 750 μg/ml and 4.61 days for 1,000 μg/ml concentrations. The finding would enable one to contemplate development of a microbial pesticide using this novel Enterobacter sp. DD01 for control of the leaf rolling pest.     

Effects of Restraint Stress on Iron,Zinc, Calcium,and Magnesium Whole Blood Levels in Mice

Objective Study the effects of acute and chronic restraint stress on the whole blood concentrations of iron (Fe), zinc (Zn), calcium (Ca), and magnesium (Mg) in mice. Materials and methods Single or repeat restraints were applied to mice to induce acute or chronic stress. The levels of elements in whole blood were determined by flame atomic absorption spectrometry. Results The levels of Fe, Zn, Ca, and Mg in blood in the acute-stress group were 351, 5.05, 60, and 44 μg/ml, respectively, and those in the corresponding control group were 391, 5.90, 59, and 45 μg/ml, respectively. The levels of blood Fe, Zn, Ca, and Mg in the chronic-tress group were 291, 3.62, 59, and 40 μg/ml, respectively, and those in the corresponding control group were 393, 4.82, 48, and 43 μg/ml, respectively. The levels of Fe and Zn in the blood of both the acute-stress and the chronic-stress groups were significantly lower (P < 0.05) than that in the control groups. The Ca level in whole blood was significantly (P < 0.05) higher in the chronic-stress group than that in the control group. Conclusion Acute and chronic restraint stress can cause changes in blood levels of Fe and Zn in mice.     

Temperature-dependent phosphate solubilization by cold- and pH-tolerant species of Aspergillus isolated from Himalayan soil

Ten species of Aspergillus isolated from soil samples collected from different locations in the Indian Himalayan region have been studied for their growth requirements and tricalcium phosphate solubilization at different temperatures. The Aspergillus species could grow at low temperature and tolerated a wide range of pH. Phosphate solubilization by various Aspergillus species ranged between 374 μg/ml (A. candidus) to 1394 μg/ml (A. niger) at 28°C, 33 μg/ml (A. fumigatus) to 2354 μg/ml (A. niger) at 21°C, 93 μg/ml (A. fumigatus) to 1452 μg/ml (A. niger) at 14°C, and 21 μg/ml (A. wentii) to 83 μg/ml (A. niger) at 9°C. At 21 and 28°C, phosphate solubilization showed a decrease within 4 weeks of incubation, whereas at 9°C and 14°C, it continued further up to 6 weeks of incubation. In general, phosphate solubilization by different Aspergillus species was recorded at a maximum of 28°C or 21°C; biomass production was favored at 21°C or 14°C. Conversely, A. nidulans and A. sydowii exhibited maximum phosphate solubilization at 14°C and produced maximum biomass at 21°C. Data suggest that suboptimal conditions (higher or lower temperature) for fungal growth and biomass production were optimal for the production of metabolites involved in phosphate solubilization. Significant negative correlations were obtained between pH and phosphate solubilization for eight species at 28°C, for seven at 21°C, and for nine at 14°C. Extracellular phosphatase activity was exhibited only in case of A. niger, whreas intracellular phosphatase activity was detected in all species, the maximum being in A. niger. Statistically significant positive or negative correlations were obtained between phosphate solubilization and other parameters in most cases at different temperatures.     

In Vitro Susceptibility of Chlamydia pecorum to Macrolides,Tetracyclines, Quinolones and β-Lactam

The in vitro susceptibility of Chlamydia pecorum to two macrolides (clarithromycin and erythromycin), two tetracyclines (doxycycline and minocycline), two quinolones (ofloxacin and ciprofloxacin) and one β-lactam (ampicillin) was determined. The MICs were 0.004 to 0.008 μg/ml for clarithromycin, 0.008 to 0.031 μg/ml for doxycycline and minocycline, 0.063 to 0.125 μg/ml for erythromycin, 0.25 to 0.5 μg/ml for ofloxacin and 0.25 to 1.0 μg/ml for ciprofloxacin. The MIC for ampicillin was greater than 1,024 μg/ml. The results show clarithromycin and doxycycline are the two most effective drugs against C. pecorum.     

Phenolic acids reduce the genotoxicity of acridine orange and ofloxacin inSalmonella typhimurium

Naturally occurring plant phenolics,p-coumaric acid (PA), caffeic acid (CA), ferulic acid (FA) and gentisic acid (GA) (25–100 nmol/L) had protective effects on acridine orange (AO; 216 μmol/L)- and ofloxacin (3 μmol/L)-induced genotoxicity inSalmonella typhimurium. FA, GA and CA exhibited a significant concentration-dependent protective effect against the genotoxicity of AO and ofloxacin, with the exception of PA, which at all concentrations tested abolished the AO and ofloxacin genotoxicity. UV spectrophotometric measurements showed the interaction of PA, FA, GA and CA with AO but not with ofloxacin; this interaction is obviously responsible for the reduction of AO-inducedS. typhimurium mutagenicity. In the case of ofloxacin the antimutagenic effect of PA, FA, GA and CA is assumed to be a result of their ability to scavenge reactive oxygen species (ROS) produced by ofloxacin.     

Concentration-dependent differntial effects of cortisol on synthesis of α-lactalbumin and of casein in cultured mouse mammary gland explants: Importance of prolactin concentration

Summary Cortisol was previously shown to elicit a concentration-dependent inhibition of α-lactalbumin accumulation in midpregnant mouse mammary gland cultured in medium containing optimal concentrations of 5 μg/ml prolactin and insulin. In contrast, casein accumulation under these conditions was progressively stimulated by addition of increasing amounts of cortisol (Ono, M.; Oka, T. Cell 19: 473–480; 1980). In the present study we found that in the presence of a suboptimal concentration of 0.5 μg/ml prolactin, 2.8×10⁻⁹ M to 2.8×10⁻⁷ M cortisol stimulated α-lactalbumin accumulation. Furthermore, higher concentrations of cortisol produced a smaller inhibition of α-lactalbumin accumulation as compared to that obtained in cultures containing 5 μg/ml prolactin. The maximal increase in α-lactalbumin accumulation attained in the presence of 1.4×10⁻⁸ M cortisol, 0.5 μg/ml prolactin, and insulin was comparable to that observed in culture containing 5 μg/ml prolactin and insulin. Similar results were obtained in a cortisol concentration-response study of α-lactalbumin accumulation in cultures containing a suboptimal concentration of 0.5 μg/ml human placental lactogen. Measurement of the rate of α-lactalbumin synthesis in cultured tissue indicated that the opposing effects of low and high concentrations of cortisol on α-lactalbumin accumulation involved an alteration in the rate of synthesis of the milk protein. In contrast to α-lactalbumin, the synthesis of casein was stimulated in a concentration-dependent manner by addition of cortisol that acted synergistically with either 0.5 μg/ml or 5 μg/ml prolactin. The maximal increases were obtained in the presence of 2.8×10⁻⁶ M cortisol. These results indicated that the action of cortisol on α-lactalbumin accumulation can be modulated by the concentration, of prolactin and suggest that the interplay between cortisol and prolactin in regulation of α-lactalbumin synthesis may be different from that involved in casein synthesis.     

Inhibition ofPseudomonas aeruginosa alginate expression by subinhibitory concentrations of antibiotics

The effects of subinhibitory concentrations (1/4, 1/8, 1/16 of the MIC) of quinolones (ciprofloxacin, enoxacin, nalidixic acid, norfloxacin, ofloxacin, pefloxacin), aminoglycosides (amikacin, gentamicin, netilmicin, streptomycin, tobramycin), β-lactams (aztreonam, ceftazidime, imipenem, ticarcilin) and macrolides (erythromycin, roxitromycin) on the excretion of alginate by aP. aeruginosa strain were studied. Both β-lactam and macrolide antibiotics were found ineffective at the concentrations tested, except erythromycin and imipenem at 1/4 MIC. Aminoglycosides at a concentration of 1/4 MIC reduced most effectively the excretion of alginate. Quinolones were also effective at this sub-MIC; 1/16 MIC was ineffective with all antibiotics or stimulated the production of alginate.