In vitro activity of lomefloxacin (SC-47111) against enterobacteriaceae, enterococci and staphylococci

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 microgram/ml in 2 species, 0.25 microgram/ml in 6, 0.125 microgram/ml in 4, and lower than 0.125 microgram/ml in 8. Slightly higher values were obtained for Serratia marcescens (2 micrograms/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 micrograms/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 micrograms/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 micrograms/ml, respectively. It was bactericidal at the MIC for 62% of the strains and at twofold the MIC for all the others.     

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.     

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.     

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.     

Comparative in vitro potency and kill curve activity of tedizolid and linezolid against Gram-positive bacteria isolated from Chinese hospitalized patients in 2013–2016

We compared the kill-curve activity of tedizolid and linezolid at clinically relevant (total or free plasma, lung) concentrations against methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae (PRSP) isolated from Chinese patients. Tedizolid had greater in vitro potency than linezolid against staphylococci, streptococci and enterococci species (tedizolid minimum inhibitory concentration (MIC) range: ≤ 0.016–0.5?µg/mL; linezolid MIC range: 0.25–2?µg/mL). In kill-curve experiments, growth of MRSA was inhibited at tedizolid concentration of 0.6?µg/mL (i.e. 4.8 × MIC; MIC = 0.125?µg/mL) and linezolid concentration of 2?µg/mL (2× MIC; MIC = 1?µg/mL). Against PRSP, tedizolid at a concentration of 0.25?µg/mL (representing its MIC) was bacteriostatic, but exerted a bactericidal effect at higher concentrations. Results were similar for linezolid, however, even at 21?µg/mL, a small proportion of organisms survived beyond 24?h. The results demonstrated the potency of tedizolid against clinical strains of Gram-positive pathogens supporting its use as a suitable alternative to linezolid in Chinese patients.     

Comparative antimicrobial spectrum and activity of BMS284756 (T-3811; a desfluoroquinolone) tested against an international collection of staphylococci and enterococci, including in vitro test development and intermethod comparisons

The study was initiated to determine the in vitro activity and MIC/disk test comparisons of BMS284756, a new des-fluoro(6)-quinolone, against isolates of staphylococci and enterococci from the SENTRY Antimicrobial Surveillance Program, 2000. Isolates were tested by reference broth microdilution and standardized disk diffusion methods. Against 3,789 strains of gram-positive cocci from the SENTRY Program (2000), the BMS284756 MIC90 and percentage susceptible at < or = 2 and < or = 4 microg/ml were: Staphylococcus aureus (4 microg/ml; 89.3 and 97.1%), coagulase-negative staphylococci (CoNS; 4 microg/ml; 86.1 and 96.0%) and enterococci (> 4 microg/ml; 62.0 and 76.2%). Also tested were selected staphylococci (300 strains) and enterococci (102 strains) by two standardized methods. The activity of BMS284756 was highly correlated with oxacillin resistance among staphylococci. Oxacillin-susceptible staphylococci were all inhibited by BMS284756 at < or = 0.5 microg/ml, whereas oxacillin-resistant strains required inhibitory concentrations of > or = 1 microg/ml. Excellent correlation was observed between the MIC and 5-microg disk zone diameter for staphylococci and enterococci (r=0.91 to 0.93). Among vancomycin-susceptible enterococci, 67% of Enterococcus faecalis, 25% of E. faecium, and 76% of other Enterococcus spp. isolates were inhibited by BMS284756 at < or = 2 microg/ml. All vancomycin-resistant enterococci (VRE; 11 E. faecalis and 15 E. faecium) were inhibited by > or = 2 microg/ml of BMS284756. Among the non-VRE, non-faecium enterococcal isolates (n=64), 62% were inhibited by < or = 0.5 microg/ml. BMS284756 showed excellent activity against oxacillin-susceptible staphylococci and moderate activity against enterococci other than VRE and E. faecium. Acceptable correlations were observed between MIC and disk test results for both tested genus groups.     

Susceptibility of Ureaplasma urealyticum to tetracycline, doxycycline, erythromycin, roxithromycin, clarithromycin, azithromycin, levofloxacin and moxifloxacin

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 MIC(50) and MIC(90) 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 MIC(90)). 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.     

In- Vitro Susceptibility of Borrelia burgdorferi and Borrelia hermsii to Ten Antimicrobial Agents

Summary

The in-vitro activity of ten antimicrobial agents against four strains of Borrelia burgdorferi originating both in the United States and Europe and against one isolate of B. hermsii was investigated. Ceftriaxone, erythromycin and roxithromycin were the most active drugs against both Borrelia species studied, with minimum bactericidal concentrations ranging from 0.015 μg/ml to 0.125 μ/ml.     

Comparative In- Vitro Activity of Fourteen Antibiotics Against Clinical Isolates of Enterococci

Summary

The in-vitto antibacterial activities of fourteen antimicrobial agents, including ampicillin, amikacin, Augmentin, ceftazidime, cefotaxime, ceftriaxone, ciprofloxacin, erythromycin, gentamicin, penicillin G, piperacillin, rifampicin, streptomycin and vancomycin, were compared against 195 enterococcal strains isolated from clinical specimens received at the King Abdulaziz University Hospital in Saudi Arabia. The antibacterial susceptibility was determined by the minimal inhibitory concentration (MIC) using an agar dilution method. Ampicillin, Augmentin and vancomycin exhibited the greatest activity, inhibiting 90% of the tested strains (MIC90) at 2 μg/ml, followed by penicillin G and piperacillin with MIC90 of 4 μg/ml. Erythromycin, third generation cephalosporins, aminoglycosides and rifampicin, on the other hand, had poor activity against enterococci with MIC90s well above the obtainable serum concentrations. The clinical implications of resistance to aminoglycosides and the alternative antimicrobial therapy in serious entrococcal infections are discussed in the text.     

In Vitro Antifungal Activity of Sertaconazole Against 309 Dermatophyte Clinical Isolates

Abstract

Three hundred and nine strains belonging to 11 species of dermatophyte moulds were tested against sertaconazole following mainly the National Committee for Clinical Laboratory Standards (M38-P) for filamentous fungi. However, several important factors such as the temperature (28°C vs 35°C) and time of incubation (4-10 d vs 21-74 h), have been modified. Sertaconazole was active against all the clinically important dermatophyte moulds involved in human infections tested. Overall geometric mean MIC of sertaconazole was 0.21 μg/ml with a MIC range of 0.01-8 μg/ml. MIC₅₀ and MIC₉₀ were respectively of 0.25 and 1 μg/ml. Sertaconazole was very active against Epidermophyton floccosum, Trichophyton rubrum, Trichophyton tonsurans and Microsporum canis (geometric means 0.08, 0.13, 0.13 and 0.19 μg/ml respectively). Microsporum audouinii had the lowest susceptibility in the study (geometric mean 0.59 μg/ml). Considering MIC₅₀ and MIC₉₀ these differences were significantly in favor of the activity of sertaconazole against E. floccosum (0.06 and 0.5 μg/ml respectively).     

Comparative In Vitro Activity of Cefepime against Nosocomial Isolates

Abstract

Cefepime, a new parenteral cephalosporin, was evaluated for its In Vitro antibacterial activity in comparison with other broad-spectrum antibiotics against a total of 445 recently isolated microorganisms of nosocomial origin. Cefepime was highly active against all species of Enterobacteriaceae with minimum inhibitory concentrations (MIC₉₀s) ranging from 0.25-8 μ/ml. Cefepime showed moderate activity against Acinetobacter spp (MIC₅₀ and MIC₉₀, 16 μ/ml) but its activity was superior to that of any drug tested, except imipenem. Against Pseudomonas aeruginosa its activity was comparable to that of ceftazidime and was greater than that of cefotaxime, aztreonam, ciprofloxacin and aminoglycosides. Of all the agents tested, imipenem was the most active compound. Cefepime was active against Staphylococcus aureus and coagulase-negative methicillin-susceptible staphylococci but it had no activity against methicillin-resistant staphylococci and enterococci.     

ZAAPS Program results for 2010: an activity and spectrum analysis of linezolid using clinical isolates from 75 medical centres in 24 countries

Abstract

The Zyvox® Annual Appraisal of Potency and Spectrum (ZAAPS) Program monitors the in vitro activities of linezolid and comparator agents for Gram-positive organisms in Latin America, Europe, Canada, and the Asia-Pacific. For the 2010 Program a total of 6305 Gram-positive strains were collected from 75 medical centres on five continents (24 countries). Reference broth microdilution susceptibility tests were performed on organisms from the following groups: Staphylococcus aureus (2875), coagulase negative staphylococci (CoNS) (855), enterococci (787), Streptococcus pneumoniae (926), viridans group and other streptococci (325), and beta-haemolytic streptococci (507). Linezolid demonstrated a 99·81% susceptibility rate among 6305 strains tested from 24 nations. Of the resistant isolates, four linezolid-resistant strains of enterococci (two each for Enterococcus faecalis and Enterococcus faecium) were found in four nations (China, Thailand, Germany, and Brazil). Eight CoNS (Staphylococcus epidermidis, Staphylococcus hominis) isolates were observed to be resistant to linezolid (MIC, ≧8 μg/ml). Two strains from Mexico were determined to be from an ongoing epidemic, and investigations showed that isolates from Italy and Brazil were also from circulating resistant clones discovered in earlier years. MRSA rates varied by region and between nations, as did resistances to other potential therapeutic agent options frequently listed for MRSA therapy such as clindamycin, fluoroquinolones and trimethoprim/sulfamethoxazole. In summary, the 2010 ZAAPS Program demonstrated that linezolid activity remains stable around the world with >99% susceptibility.     

Successful Treatment of an Aspergillus fumigatus Infection with Voriconazole Via a Nasogastric Tube

Abstract

Extended-spectrum beta-lactamase (ESBL) production by Enterobacteriaceae is an emerging problem. This 3-year prospective study was undertaken to determine the prevalence of such enzymes among the clinically significant isolates of the Enterobacteriaceae family gathered from patients, and to evaluate the different techniques for their detection as well as their clinical significance. Members of the Enterobacteriaceae family isolated from blood, inhibited by the third-generation cephalosporins with minimum inhibitory concentrations (MICs) of ≤2 μg/ml and MIC ≤8 μg/ml and isolates from other sources inhibited by MIC ≤8 μg/ml were also investigated for ESBL production by VITEK2 and E test. Their clinical significance in septicemic patients was analyzed. Out of 3,215 isolates, 1018 (31.7%) were ESBL-producers by both VITEK2 and E test. Of these, 428 (42%) were Klebsiella pneumoniae and 376 (37.0%) were Escherichia coli with overall prevalence rates of 13.3% and 11.7%, respectively. There were a total of 184 septicemic patients infected by ESBL-producing Enter-obacteriaceae out of which 134 (73%) needed modification of therapy; most (58%) of these patients were initially on third-generation cephalosporin therapy. A total of 58 (31.5%) patients were infected by ESBL-producing blood isolates which were inhibited by cefotaxime/ceftriaxone at MICs ≤8 μg/ml (within the susceptibility range). Resistance to both aminoglycosides and quinolones were significantly higher among ESBL-producing isolates compared to non-producers (P<0.05). This study highlights a high prevalence of ESBL-producing Enterobacteriaceae in a major tertiary teaching hospital in our country and demonstrates that almost a third of the ESBL-producing Enter-obacteriaceae blood isolates would have been released as susceptible by routine susceptibility testing; a finding inimical to optimal therapeutic success.     

The Integration of Four Major Determinants of Antibiotic Action: Bactericidal Activity,Postantibiotic Effect,Susceptibility, and Pharmacokinetics

Abstract

A functional pharmacokinetic/pharmacodynamic (PK/PD) index that could simultaneously describe three controlling PD variables, i.e., bactericidal activity, postantibiotic effect (PAE), and susceptibility, in relation to pharmacokinetics, was designed using an in vitro kinetic model. Tobramycin was tested against one standard and five clinical strains of Pseudomonas aeruginosa. The organisms showed minimum inhibitory concentrations (MICs) ranging between 1 and >1000 μg/ml. The model allowed antibiotic concentrations to be reduced exponentially from initial concentrations at fixed multiples of MIC. Antibiotic removal was performed when the decreasing concentrations hit the MIC of individual strain to provide a wide range of AUC_>MIC within an identical frame of AUC_>MIC/MIC (AUIC) values. Viable counts were measured at antibiotic addition and before/after its removal for bactericidal activity and PAE assessments. A linear relationship was observed between PAE and bactericidal rate constants, though the pattern varied among different strains. Characterization of the exposure (AUC_>MIC)-effect relationships using the E_max model revealed that the less susceptible strains displayed lower E_max and higher EC₅₀ for both antimicrobial effects. By employing the AUIC as a common frame of reference, regression analysis showed a significant linear correlation (p<0.05) between the mean PAE and bactericidal rate data and, thereby simultaneously defining the four contributing factors of the PK/PD system. It appears that the AUIC, by conveying the pharmacokinetic and susceptibility information, could serve as a PK/PD index in bridging the interdependency of PAE and bactericidal activity. More importantly, the collective assessment of these four factors would allow more optimal evaluation of dosage regimens.     

In vitro evaluation of ertapenem (MK-0826), a long-acting carbapenem, tested against selected resistant strains

Ertapenem (MK-0826) is a novel, long-acting parenteral carbapenem. The purpose of this in vitro study was to test ertapenem's activity against a collection of multiply-resistant strains of gram-positive and -negative bacteria isolated from locations worldwide, and to examine its bactericidal activity and ability to act in a synergistic manner in combination with other antimicrobial agents. Ertapenem was active against a variety of gram-negative pathogens, with particular potency noted for Escherichia coli and Klebsiella pneumoniae (MIC90s < or =0.015-0.5 microg/mL) including extended spectrum beta-lactamase producing strains. Less ertapenem activity was seen against Pseudomonas aeruginosa, especially ceftazidime-resistant strains (MIC50 16 microg/mL). Except for enterococci, ertapenem was active against most gram-positive species, including beta-haemolytic streptococci (MIC90 0.03 microg/mL; 100% susceptible), viridans group streptococci (MIC90 2 microg/mL; 98.1% susceptible), and penicillin-susceptible Streptococcus pneumoniae (MIC90 < or =0.015 microg/mL; 100% susceptible). Ertapenem was also very potent against Haemophilus influenzae (MIC90 0.25 microg/mL; 100% susceptible). Bactericidal action was observed versus staphylococci, E. coli, and K. pneumoniae, and at least an additive effect was detected against the majority of the strains tested when ertapenem was combined with ciprofloxacin or gentamicin. These results from testing 902 organisms indicate that ertapenem appears to be a promising broad-spectrum carbapenem with a possible role against some emerging resistant species.     

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).     

In Vitro Activity of Clarithromycin Against Penicillin-Susceptible and Penicillin-Resistant Strains of Streptococcus pneumoniae in a Pharmacodynamic Simulation Model

Abstract

Clarithromycin has shown enhanced activity against Streptococcus pneumoniae, but increased resistance to macrolides has been observed in recent years. Our aim was to investigate its activity against strains of S. pneumoniae with variable susceptibility to this antibiotic and to penicillin. We determined killing curves using the Centriprep-10 pharmacodynamic simulation model, which permits using varying antibiotic concentrations to mimic a pharmacoki-netic human profile in serum (corresponding to an oral dose of 500 mg). Four strains of S. pneumoniae were tested. In susceptible strains, clarithromycin showed bactericidal activity (reductions of up to 2.97 log₁₀ cfu/ml of the initial inoculum). In resistant strains, clarithromycin showed a bacteriostatic effect (<1 log₁₀ cfu/ml reduction). Penicillin-susceptible strains showed higher reductions than penicillin-resistant strains. This effect is important owing to the high minimum inhibitory concentration (MIC) of one of the resistant strains (32 μg/ml). More studies are needed to explain this bacteriostatic activity.     

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.     

Daptomycin In Vitro Activity Tested Against Gram-Positive Strains Collected from European and Latin American Medical Centers in 2003

Abstract

Daptomycin, a cyclic lipopeptide, was susceptibility tested against clinical bacterial isolates consecutively collected in hospitals located in Europe (4,731 strains) and Latin America (1,007 strains) in 2003 as part of a continuing surveillance program. The bacterial isolates tested were Gram-positive pathogens that included staphylococci, streptococci and enterococci. The isolates were tested for susceptibility using broth microdilution methods (broth with 50 mg/L Ca⁺⁺ for testing daptomycin). All isolates, except two Enterococcus faecium strains from Europe, were inhibited at daptomycin MIC of ≤4 mg/L. In addition, 99.4 and 97.3% of isolates were inhibited at daptomycin MIC of ≤2 and ≤1 mg/L, respectively. Except for one Staphylococcus aureus and one viridans group streptococci from Europe and one coagulase-negative staphylococci from Latin America, all staphylococcal and streptococcal isolates were inhibited by 1 mg/L of daptomycin. Resistance to other compounds (vancomycin, oxacillin, and penicillin) did not influence daptomycin activity. The activity of daptomycin was very similar in both geographic regions evaluated and demonstrated the same MIC distribution as isolates evaluated in studies in the United States. The results of this study showed that daptomycin continues to be very active against clinical isolates of Gram-positive cocci isolated in Europe and Latin America.     

In vitro activities of antimicrobial cationic peptides; melittin and nisin,alone or in combination with antibiotics against Gram-positive bacteria

Abstract

The in vitro activities of two antimicrobial cationic peptides, melittin and nisin alone and in combination with frequently used antibiotics (daptomycin, vancomycin, linezolid, ampicillin, and erythromycin), were assessed against clinical isolates of methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus and Enterococcus faecalis. Using the broth microdilution method, minimum inhibitory concentration (MIC) ranges of melittin and nisin against all strains were 2–8 μg/ml and 2–32 μg/ml respectively. In combination studies performed with the microdilution checkerboard method using a fractional inhibitory concentration index of ?0·5 as borderline, synergistic interactions occurred more frequently with nisin–ampicillin combination against MSSA and nisin–daptomycin combination against E. faecalis strains. The results of the time-killing curve analysis demonstrated that the concentration dependent rapid bactericidal activity of nisin, and that synergism or early synergism was detected in most strains when nisin or melittin was used in combination with antibiotics even at concentrations of 0·5×MIC.