Bactericidal activity of Pistacia lentiscus mastic gum against Helicobacter pylori.

In this study we evaluated the antibacterial activity of mastic gum, a resin obtained from the Pistacia lentiscus tree, against clinical isolates of Helicobacter pylori. The minimal bactericidal concentrations (MBCs) were obtained by a microdilution assay. Mastic gum killed 50% of the strains tested at a concentration of 125 microg/ml and 90% at a concentration of 500 microg/ml. The influence of sub-MBCs of mastic gum on the morphologies of H. pylori was evaluated by transmission electron microscopy. The lentiscus resin induced blebbing, morphological abnormalities and cellular fragmentation in H. pylori cells.     

Interference on Helicobacter pylori Growth and Adhesion by Omeprazole and Other Drugs

Abstract

Helicobacter pylori is the causative agent of gastritis and a co-agent in other gastroduodenal diseases. Gastroduodenal ulcer and MALT-lymphoma in particular, regress when patients are administered antimicrobial agents to eradicate infection. Sometimes eradication is not definitive and is difficult to check. The aim of our study was to test the antimicrobial activity of omeprazole on H. pylori in comparison with ampicillin and other anti-H₂ drugs (ranitidine and famotidine), and to evaluate their interference with bacterial adhesion of H. pylori. We also compared results of the agar dilution antibacterial sensitivity test on H. pylori to those obtained using a bacteria adherence to cell monolayers model, to see if drug activity was different against adhered bacteria. We evaluated omeprazole and ampicillin MIC90s (minimum inhibitory concentrations) against 20 H. pylori isolates by traditional agar dilution method and by exposing previously adhered bacteria to an Hep-2 monolayer to different drug concentrations. The activity against bacteria adhered to cell lines was evaluated by counting viable adhered bacteria after 1, 6, 12 hours of contact with drug. Interference with adherence to Hep-2 cells was also tested. Omeprazole and ampicillin MICs were comparable to other findings (omeprazole MIC90 was 12.5 μg/ml and ampicillin MIC90 was 0.016 μg/ml), while higher concentrations were necessary (4 × MIC90) against adhered bacteria. These findings suggest that MICs evaluated with traditional assays can have different predictivity than tests on adhered H. pylori.     

In Vitro Activity of Lomefloxacin (SC-47111) Against Enterobacteriaceae,Enterococci and Staphylococci

Summary

The activity of lomefloxacin, a new difluorinated quinolone, was tested against 190 Enterobacteriaceae strains (belonging to 23 different species), 70 enterococci and 70 staphylococci. As regards Enterobacteriaceae, the activity of lomefloxacin was the same as that of norfloxacin in 9 out of the 23 species tested, and only slightly lower in further 8 species. Minimum inhibitory concentrations (MIC) values for 90% of strains were 0.5 μg/ml in 2 species, 0.25 μg/ml in 6, 0.125 μg/ml in 4, and lower than 0.125 μg/ml in 8. Slightly higher values were obtained for Serratia marcescens (2 μg/ml), whilst, as already reported for the other new quinolones, the susceptibility of the Providencia genus was very poor, with MIC values up to 128 μg/ml for the vast majority of strains. Lomefloxacin proved bactericidal at the MIC in all the Enterobacteriaceae strains tested but 20. In the latter strains, however, bactericidal activity could be appreciated at values slightly exceeding MIC. As regards enterococci, the MIC for 90% of strains was 32 μg/ml. Minimum bactericidal concentration (MBC) was the same as the MIC for 78% of the strains tested and was only twofold higher in all the others. The new drug was also active against staphylococci having an MIC50 and MIC₉₀ of 0.5 and 2 μg/ml, respectively. It was bactericidal at the MIC for 62% of the strains and at twofold the MIC for all the others.     

Inhibitory and Bactericidal Activity of Rokitamycin against Helicobacter pylori and Morphological Alterations

Abstract

Rokitamycin is a macrolide antibiotic, recently entered into clinical use. Its in vitro activity and kill kinetics against Helicobater pylori have been evaluated at 1 x the minimum inhibitory concentration (MIC), 2×MIC and 4×MIC at 2, 4, 8, 24 hours and compared with those of clarithromycin, erythromycin and amoxicillin. Morphological changes in H. pylori induced by rokitamycin incubation at these MICs and times were also investigated by scanning electron microscopy. All the antibiotics tested had good inhibitory activity against H. pylori, a slow growing microorganism. The order of MIC activity was clarithromycin > amoxicillin > rokitamycin > erythromycin. Rokitamycin killed more rapidly than the other antibiotics, in fact H. pylori strains were totally killed at 8 h (2×MIC) and 4 h ( 4×MIC) and after only 2h incubation all concentrations greatly decreased the CFU/ml. These effects were also confirmed by the rapid appearance of surface and morphological alterations (focal blebs, constrictions, rounded forms) in the normal structure of H. pylori observed by scanning electron microscopy. Clinical studies should be conducted to investigate the in vivo activity of rokitamycin, as an agent to be used in the combination therapies against H. pylori.     

In Vitro Activity of Cefpirome (HR 810) against Enterococci and Staphylococci

Summary

The inhibitory activity of cefpirome (HR 810), a new cephalosporin derivative for parenteral use, was tested by agar dilution methods against Enterococcus faecatis (100 strains), Staphylococcus aureus (40 strains) and coagulase-negative staphylococcal species (60 strains) in comparison with other beta-lac ta m antibiotics.

For E. faecalls, the cefpirome minimum inhibitory concentration (MIC) range was 2-128 μg/ml, with an MIC,, of 8 μg/ml, and an MIC₉₀, of 64 μg/ml. The optimal bactericidal activity against strains with MICs of ≤ 8 μg/ml occurred at 2-4 times the MIC, and the reduction in the initial inoculum was 99.9-99.7% after 24 h incubation at these concentrations.

Mec gene-negative staphylococci (both S. aureus and coagulase- negative species) had cefpirome MICs of 0.25-2 μg/ml (MIC₅₀ 0.5 μg/ml, MIC₉₀ 1 μg/ml). Mec gene-positive strains had MICs of 0.5-128 μg/ml (MIC₅₀ 2 μg/ml, MIC₉₀ 32 μg/ml). Strains with borderline resistance to oxacillin which did not harbor the mec gene and which were susceptible to cefpirome maintained their susceptibility even when high-density inocula were used and after several passages in media containing the antibiotic.

These studies present some potential advantages of cefpirome over other cephalosporins in the inhibitory activity against Gram-positive cocci.     

In Vitro and In Vivo Antimicrobial Action of Fluphenazine

Abstract

The antipsychotic drug fluphenazine was obtained in a dry powder form and was screened with respect to 482 strains of bacteria, which included 170 Gram-positive and 326 Gram-negative strains. Nutrient agar plates containing increasing concentrations of fluphenazine (0-200 μg/ml) were used for the determination of the minimum inhibitory concentration (MIC) which was demonstrated by inoculating a loopful of an overnight peptone water culture of the organism on nutrient agar plates and determining the MIC against a control. Fluphenazine was detected to possess pronounced action against both Gram-positive and Gram-negative bacteria at 20-100 μg/ml. In the In Vivo studies it was seen that when fluphenazine was used at a concentration of 1.5 μg/g and 3 μg/g mouse body weight both the levels offered significant protection to Swiss strain of white mice when challenged with 50 minimum lethal dose (MLD) of a virulent strain of Salmonella typhimurium 74. The In Vivo data with fluphenazine were highly significant (p <0.001) according to the chi-square test.     

A Pharmacodynamic Model to Support a 12-Hour Dosing Interval for Amoxicillin/Sulbactam,a Novel Oral Combination,in the Treatment of Community-Acquired Lower Respiratory Tract Infections

Abstract

We evaluated, by time-kill studies, the pharmacodynamics of amoxicillin/sul-bactam (AMX/SUL, 875 mg/125 mg), a novel oral combination, against the major respiratory pathogens in 12 volunteers receiving a single dose. The sera corresponding to 50% of a 12-h dosing interval displayed either bactericidal or inhibitory activity against both a penicillin-susceptible and a penicillin-intermediate Streptococcus pneumoniae strain (penicillin MIC of 0.03 and 0.25 μg/ml, respectively), as well as against a β-lactamase-positive Moraxella catarrhalis and a β-lactamase-negative Haemophilus influenzae strain. Both the peak samples and those corresponding to 4 h after dose (i.e. 33% of a 12-h dosing interval) proved active against both a penicillin-resistant S. pneumoniae (MIC, 2 μg/ml) and a β-lactamase-positive H. influenzae strain. The AMX-SUL formulation evaluated in this study showed pharmacodynamic features that support clinical trials to assess its efficacy in the treatment of lower respiratory tract infections with a 12-h dosing interval regimen.     

Peritoneal carcinomatosis from ovarian cancer: cytoreductive surgery and intraperitoneal chemotherapy

Abstract

We tested the in vitro bactericidal activity of moxifloxacin, a new 8-methoxyquinolone, alone and in combination with vancomycin or teicoplanin at different multiples of minimum inhibitory concentration (MIC) against 8 methicillin-ciprofloxacin-resistant Staphylococcus aureus (M-C-RSA) and 1 methicillin-ciprofloxacin susceptible S. aureus (M-C-SSA) recently isolated from device-associated infections unresponsive to or relapsing after glycopeptide therapy, despite device removal. MICs of vancomycin ranged from 1 to 4 μg/ml, MICs of teicoplanin ranged from 2 to 8 μg/ml; MICs of moxifloxacin were always 2 μg/ml against M-CRSA isolates and 0.125 μg/ml against the M-C-SSA isolate. The 9 strains resulted tolerant when tested for vancomycin, teicoplanin, and moxifloxacin used alone at 2xMIC. In all cases the combination of moxifloxacin and teicoplanin or vancomycin appeared to be bactericidal already at MIC concentration for glycopeptides plus 0.5xMIC concentration for moxifloxacin. If these results are confirmed in vivo in animal experiments, the combination of moxifloxacin with glycopeptides might be useful for treating device-associated infections, and in preventing the frightening phenomenon of increasing MICs for glycopeptides.     

Ofloxacin: In Vitro Activity Against Recently Isolated Gram-Negative Bacterial Strains

Summary

The activity of ofloxacin was determined against 117 Enter obacteriaceae, 13 Acinetobacter var. anitratus, 124 Pseudomonas aeruginosa in comparison with other antibiotics. Its activity was very high: against Enterobacteriaceae the minimum inhibitory concentration (MIC)₅₀ was 0.125 μg/ml, the MIC₉₀ lμg/ml, and the geometric mean (GM) was 0.4 μg/ml; against Acinetobacter var. anitratus the MIC₅₀ 1 μg/ml, MIC₉₀ 4 μg/ml, GM 1.7 μg/ml. Unlike other authors we found that the activity of ofloxacin was influenced by the selection of P. aeruginosa resistant to carbenicillin and gentamicin.     

Inhibition of Herpes Simplex Virus Infection by Negatively Charged and Neutral Carbohydrate Polymers

Abstract

Different natural and semisynthetic polysaccharides were evaluated for their inhibitory effect on in vitro replication of herpes simplex virus (HSV) types 1 and 2.

Some neutral and negatively charged carbohydrates were able to inhibit viral infection by interfering mainly with the adsorption process showing a dose-dependent relationship. Their effect was shown within the concentration range of 200-0.8 μg/ml, and the inhibiting compounds were in order of action: dextran sulfate = sdero-glucan = lambda carrageenan > glyloid sulfate 4324 > locust bean gum towards HSV-1 and dextran sulfate = glyloid sulfate 4324 = lambda carrageenan > scleroglucan > glycogen sulfate 4435 towards HSV-2.

The data obtained indicate that the antiviral activity of polysaccharides was not only related to their electric charge. Other characteristics of the molecules such as the polymeric backbone, the carbohydrate moieties and the degree of polymerization could play a role in influencing their antiviral properties.     

Determination of the Susceptibility In Vitro of 54 Isolates of Mycobacterium fortuitum against Three Fluoroquinolones Using Two Methods

Abstract

The In Vitro susceptibility to ofloxacin, norfloxacin and ciprofloxacin or 54 Mycobacterium fortuitum isolates originating from clinical samples (7) of patients attending the Hospital Universitario de Canarias and Hospital del Tórax, and from environmental (47) sources, were determined. For this, two methods were used: dilution in agar with Middlebrook 7H10 Agar as a base medium culture, and broth microdilution, with Mueller-Hinton Broth without supplement.

The different isolates under study revealed a uniform susceptibility by both methods against ciprofloxacin.

100% inhibition was obtained from a Minimum Inhibitory Concentration (MIC) of 0.25 μg/ml, and 2 μg/ml of ciprofloxacin, for broth microdilution and dilution in agar, respectively.

For ofloxacin and norfloxacin, all the isolates were inhibited at an MIC of 0.5 μ/ml, by the broth microdilution method, which contrasted sharply with an MIC of 32 μ/ml, in the case of dilution in agar.

In this study, we have observed the existence of differences in the In Vitro susceptibility of the isolates of M. fortuitum against the three fluoroquinolones assayed, mainly for ofloxacin and norfloxacin, by both methods. We, therefore, consider it necessary to establish a standardized, reproducible assay method, for the study of sensitivity to atypical mycobacteria.     

Pharmacokinetics and Tissue Distribution of Amoxicillin plus Clavulanic Acid after Oral Administration in Man

Summary

Alimentili (875 amoxicillin and 125 mg potassium clavulanate) was administered orally to patients with chronic bronchitis. Concentrations of amoxicillin and clavulanic acid were measured in serum, sputum and urine. Peak serum levels for amoxicillin of 11.23 ± 2.61 μg/ml were observed at 2 hours and for clavulanic acid of 2.55 ± 0.54 μg/ml at 1 hour. After 9 hours, 50% of the amoxicillin and 39% of the clavulanic acid had been renally excreted. The peak sputum concentration of amoxicillin was 1.31 ± 0.42 μg/ml at 4 hours and of clavulanate was 0.79 ± 0.23 ± μg/ml at 2 hours.

Patients awaiting surgery received an oral dose of augmentin as above. Samples of lung, tonsil, middle ear mucosa and prostate were obtained and tissue concentrations of both compounds measured. Peak levels of amoxicillin ranged from 0.87 μg/g (tonsil) to 2.56 μg/g (lung) and of clavulanic acid from 0.20 μg/g (prostate) to 0.56 μg/g (lung) between 3 and 4 hours after dosing.     

In- Vitro Susceptibility of Clinical Isolates of Pseudomonas aeruginosa to β-Lactam and Aminoglycoside Antibiotics

Summary

The in-vitro susceptibilities of 198 isolates of Pseudomonas aeruginosa from clinical human specimens were determined by an agar dilution technique against (β-lactams and aminoglycosides. These isolates were susceptible to imipenem, aztreonam and ceftazidime with the minimum inhibitory concentration (MIC) for 90% of the strains tested being 8, 16 and 8 μg/ml, respectively. Aminoglycosides, except amikacin, had low activity (MIC90 > 128 μg/ml).     

Activity of Aztreonam in Pneumology,Part 2: Influence on Phagocytosis and Intracellular Killing of Human Alveolar Macrophages

Summary

The study aim was to evaluate the activity of aztreonam on phagocytosis and intracellular killing of Staphylococcus aureus ATCC6538 by human alveolar macrophages. Drug concentrations of 1, 10, 25, 100 μg/ml were assayed in culture medium.

Aztreonam induces dose-dependent phagocytosis up to 25 μg/ml concentrations; with a phagocytosis index (PIa) of 1.18 ± 0.2 at 1 μg/ml; of 1.27 ± 0.2 at 10 μg/ml; of 1.42 ± 0.3 at 25 μg/ml. No phagocytosis increase or inhibition, with unchanged cell viability compared to controls, is shown at 100 μg/ml aztreonam (PI 1.03 ± 0.3). Intracellular killing acts in a similar way: the killing index (KIa) is 1.27 ± 0.3 at 1 μg/ml concentrations; 1.38 ± 0.3 at 10 μg/ml; 1.61 ± 0.4 at 25 μg/ml whereas at 100 μg/ml the KIa is 1.03 ± 0.3. This study shows aztreonam's ability to stimulate macrophages' functional activity against a microorganism (S. aureus) which is not susceptible to its antibacterial activity.     

Antitumor activity of delocalized lipophilic cation, MKT-077 in human carcinomas obtained from fresh surgical specimens

Background. MKT-077, a delocalized lipophilic cation, accumulates in mitochondria according to the negative potential inside the mitochondria and exerts cytotoxicity. We investigated the antitumor activity and spectrum of MKT-077 in fresh surgical specimens. Methods. Single cell suspensions of fresh surgical specimens obtained from patients with gastric, colon, and hepatocellular carcinoma were treated with MKT-077 at a cutoff concentration of 30 μg/ml. Cell viability was detected by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay. Results. When the cutoff concentration was 30 μg/ml, the efficacy rates (sensitive cases/evaluated cases in percent) of MKT-077 were 52.6% for gastric cancer, 77.8% for colon cancer, and 35.7% for hepatocellular carcinoma, resulting in an overall efficacy rate of 52.4% (22/42). This was higher than the rates for other agents, including mitomycin C, doxorubicin, 5-fluorouracil, and cisplatin. The antitumor spectrum of MKT-077 was correlated with that of doxorubicin, while the antitumor spectra of mitomycin C, 5-fluorouracil, and cisplatin were completely independent of that of MKT-077. Conclusion. Since MKT-077 seemed to have a different antitumor spectrum from that of the conventionally available agents, further investigation should be conducted, including studies of the combined effect of MKT-077 and other antitumor agents. Received: June 24, 1998 / Accepted: November 20, 1998     

Effects of Aspergillus terreus Extract on Herpes Simplex 1 Virus Replication

Abstract

In this study we reported about the antiviral activity of Aspergillus terreus alcohol extract against Herpes simplex type 1 virus. This activity is dose-dependent, is related to the concentration of the challenging virus and depends particularly on a proteic fraction of 5-10 Kda. Optimal effects were observed with doses ranging from 25 to 6.25 μg/ml for crude alcohol extract and up to 3 μg/ml for 5-10 Kda fraction. Moreover, antiviral activity was evident in viral replication, but not on virus out of the cells. An increased ³H thymidine incorporation was noted on infected cells treated with the extract and this effect may suggest an intracellular accumulation of viral DNA in the absence or reduction of virion production.     

Mechanism of antitumor action of PKC activator,gnidimacrin

Daphnane-type diterpene gnidimacrin isolated from the Chinese plant Stellera chamaejasme L. is an antitumor agent that activates protein kinase C (PKC). The mechanism of antitumor action of gnidimacrin and the possible involvement of PKC were examined using sensitive K562 and refractory HLE cells. Gnidimacrin did bind to K562 cells 3 times more than to HLE cells. Immunoblot analyses revealed pronounced PKCβII expression in gnidimacrin sensitive cell lines including K562 cells, while refractory HLE cells strongly expressed PKCα, but not PKCβII. In a 24-hr exposure of K562 cells to gnidimacrin, G₁ phase arrest and inhibition of cdk2 kinase activity was found at growth-inhibitory concentration (0.0005 μg/ml). Complete inhibition of cdk2 activity and maximum G₁ phase arrest were observed at 0.005 μg/ml, however, these biological effects were reduced at 0.05 μg/ml (260 times the 50% inhibitory concentration). Cellular PKC after a 24-hr exposure was examined by immunoblot analysis and specific binding of [³H]phorbol-12,13-dibutyrate as a ligand of PKC. Expression and the amount of functional PKC of K562 cells were not changed at 0.002 μg/ml, but down-regulated to less than 1/10th of the control at 0.05 μg/ml. The reduction of biological effects at 0.05 μg/ml is most likely due to PKC down-regulation. Our results suggest that PKC (particularly βII) is one of the major determinants of the ability of cells to respond to gnidimacrin and that the antitumor action might be associated with cell-cycle regulation through suppression of cdk2 activity. Int. J. Cancer 77:243–250, 1998.© 1998 Wiley-Liss, Inc.     

Mutations affecting domain V of the 23S rRNA gene in Helicobacter pylori from Cairo,Egypt

Background: Clarithromycin is a main component of the recommended first-line triple therapy for Helicobacter pylori in Egypt. We aimed in our study to investigate the prevalence of clarithromycin-resistant H. pylori strains due to the point mutations at domain V of the H. pylori 23S rRNA among the Egyptian population using the polymerase chain reaction/restricted fragment length polymorphism (PCR/RFLP) assay.

Methods: Gastric biopsies obtained from 100 dyspeptic patients who consecutively attended at Cairo University Hospital during the period from January to November 2013 were subjected to PCR/RFLP in order to detect the point mutations at domain V of the H. pylori 23S rRNA associated with clarithromycin resistance. The PCR amplicon of the 23S H. pylori rRNA is restricted with MboII for detection of A2142G mutation and with BsaI for A2143G mutation.

Results: The prevalence of H. pylori infection among 100 patients was 70%; clarithromycin resistance was detected in 39/70 (57.7%) of positive H. pylori isolates. Occurrence of 23S rRNA A2142G mutations resulted in two DNA fragments (418 and 350?bp) by PCR-RFLP; on the other hand, no A2143G mutations were detected.

Conclusions: The high prevalence of clarithromycin resistance (57.7%) caused by A2142G mutations at domain V of the H. pylori 23S rRNA may mandate changing of the standard clarithromycin-containing triple therapy. The PCR/RFLP assay was a rapid and accurate method for molecular detection of H. pylori infection in addition to determination of different nucleotide mutations causing clarithromycin resistance.     

Involvement of non-Helicobacter pylori helicobacter infections in Helicobacter pylori-negative gastric MALT lymphoma pathogenesis and efficacy of eradication therapy

Background

Eradication therapy is known to be effective against Helicobacter pylori-positive gastric MALT lymphoma but predicting the efficacy of eradication therapy against Helicobacter pylori-negative gastric MALT lymphoma is difficult. Recent reports have shown that non-Helicobacter pylori helicobacter infections induce gastric MALT lymphoma, and we aimed to clarify whether non-Helicobacter pylori helicobacter infections are associated with the efficacy of eradication therapy.

Methods

We analyzed eradication therapy as a first-line treatment for 182 cases of gastric MALT lymphoma, classified according to Helicobacter pylori infection and API2-MALT1 mutation status. We also evaluated the non-Helicobacter pylori helicobacter infection status in 29 Helicobacter pylori-negative cases via PCR with DNA extracted from paraffin-embedded biopsy tissues. Finally, we analyzed the relationship between non-Helicobacter pylori helicobacter infection status and eradication therapy outcome.

Results

The API2-MALT1 mutation was observed in 13/182 patients (7.1%), none of whom were cured by eradication therapy. Helicobacter pylori-negative cases had a significantly higher non-Helicobacter pylori helicobacter infection rate than Helicobacter pylori-positive cases (16/29, 55% vs. 3/29, 10%; P?<?0.05). Among the Helicobacter pylori-negative cases, non-Helicobacter pylori helicobacter-positive cases had a significantly higher complete response rate than non-Helicobacter pylori helicobacter-negative cases (12/16, 75% vs. 3/13, 23%; P?<?0.05).

Conclusion

Helicobacter pylori-negative and API2-MALT1-negative gastric MALT lymphoma cases exhibited a high rate of non-Helicobacter pylori helicobacter infections, which may have contributed to the success of eradication therapy. Therefore, we recommend eradication therapy as a first-line treatment for non-Helicobacter pylori helicobacter-positive gastric MALT lymphoma.

     

Susceptibility of Ureaplasma urealyticum to Tetracycline,Doxycycline, Erythromycin,Roxithromycin, Clarithromycin,Azithromycin, Levofloxacin and Moxifloxacin

Abstract

The in vitro activity of tetracycline, doxycycline, erythromycin, roxithromycin, clarithromycin, azithromycin, levofloxacin and moxifloxacin was tested against 63 clinical isolates of Ureaplasma urealyticum. The minimal inhibitory concentrations (MICs) and the minimal bactericidal concentrations (MBCs) were determined by the broth microdilution method in A7 medium. The miC50 and miC90 of the tested agents after 24 h of incubation were as follows: Tetracycline, 0.5 and 2.0 μg/ml; doxycycline, 0.125 and 0.25 μg/ml; erythromycin, 2.0 and 8.0 μg/ml; roxithromycin, 2.0 and 4.0 μg/ml; clarithromycin, 0.25 and 1.0 μg/ml; azithromycin, 2.0 and 4.0 μg/ml; levofloxacin, 1.0 and 2.0 μg/ml; and moxifloxacin, 0.5 and 0.5 μg/ml, respectively. The MIC values after 24 h and 48 h incubation differed by no more than one dilution for all the agents with the exception of doxycycline (two dilution difference for MIC₉₀). Overall, moxifloxacin was the most active agent in vitro against U. Urealyticum, with the narrowest difference between MIC and MBC values, followed closely by levofloxacin. Clarithromycin was the most active macrolide.