In-vitro activity of nisin against clinical isolates of Clostridium difficile

Nisin is a cationic peptide produced by Lactococcus lactis. Its activity against clinical isolates of Clostridium difficile was compared to that of vancomycin and metronidazole by minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time-kill studies. Nisin was more active than the other agents, with a MIC90 of 0.256 mg/L and strong bactericidal activity. Nisin may be a promising agent for the management of C. difficile associated diarrhea.     

Comparative in vitro activity of linezolid and five other antimicrobials against nosocomial isolates of methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis and vancomycin-resistant Enterococcus faecium

The activity of linezolid in comparison to vancomycin, teicoplanin, oxacillin, clindamycin and gentamicin was tested against 60 strains of methicillin-resistant Staphylococcus aureus, 60 strains of methicillin-resistant Staphylococcus epidermidis isolated from patients with nosocomial infections and 24 strains of vancomycin-resistant Enterococcus faecium isolated from feces of hospitalized patients. Minimum Inhibitory Concentrations (MICs) were determined by the Epsilometer test method. All tested strains were sensitive to linezolid and specifically all methicillin-resistant S. aureus had MIC range 0.25-3.00, MIC50 = 0.75, MIC90 = 1.5, all methicillin-resistant S. epidermidis had MIC range 0.125-1.5, MIC50 = 0.5, MIC90 = 1 and all vancomycin-resistant E. faecium had MIC range 0.5-1.5, MIC50 = 1, MIC90 = 1. Linezolid is the first of a novel antimicrobial class, the oxazolidinones, which is a promising treatment for serious Gram-positive infections, including multiresistant strains.     

Comparative in vitro activity of quinupristin/dalfopristin and seven other antimicrobials against methicillin-susceptible and methicillin-resistant nosocomial Staphylococcus aureus bloodstream isolates

Staphylococcus aureus strains resistant to a variety of antimicrobial agents are often found in the hospital environment and are responsible for many life-threatening infections. The activity of quinupristin/dalfopristin against 84 Staphylococcus aureus bloodstream isolates (both methicillin resistant and methicillin sensitive) was compared to the activity of vancomycin, teicoplanin, erythromycin, oxacillin, clindamycin, gentamicin, rifampicin. The Minimum Inhibitory Concentrations of these agents was evaluated with the Epsilometer Test. Quinupristin/dalfopristin inhibited all methicillin-sensitive strains at 1mg/L, and 75% of methicillin-resistant strains at 1.5mg/L. According to these results, quinupristin-dalfopristin shows promising in-vitro activity and may be a welcome alternative treatment for methicillin-resistant staphylococcal infections, resulting in reduced use of glycopeptides.     

In vitro activity of linezolid and other antibiotics against Gram-positive bacteria from the major teaching hospitals in Kuwait

Multidrug-resistant Gram-positive bacteria are an increasingly pressing problem in the clinic. Consequently, linezolid, a recently introduced oxazolidinone with Gram-positive activity, was tested in comparison with 10 other antibiotics against 8103 clinically significant Gram-positive cocci by Etest, disk diffusion and Vitek methods. Linezolid demonstrated excellent activities against all isolates. Vancomycin and teicoplanin demonstrated equally excellent activity against almost all isolates. The methicillin-resistant Staphylococcus aureus (MRSA) strains were all susceptible to the glycopeptides and linezolid, but resistant to erythromycin (96%), fusidic acid (91.5%), gentamicin (84%) and clindamycin (73%). Forty one and 39% of the Streptococcus pneumoniae isolates were resistant to penicillin (MIC >0.5 microg/ml) and erythromycin (MIC >1 microg/ml), respectively. S. agalactiae susceptibility was 9% and 10% resistant to clindamycin and erythromycin, respectively. In conclusion, all the Gram-positive isolates tested were susceptible to linezolid. With its oral bioavailability profiles, it obviously holds great promise. Our data should be a useful addition to the literature from the Middle East.     

In vitro evaluation of faropenem activity against anaerobic bacteria

Faropenem, a new oral penem with broad spectrum activity, could be used as empirical treatment in infections due to unidentified anaerobes, but only a few investigations have been carried out on these bacteria. The aim of this study was to compare faropenem in vitro activity with that of positive antimicrobial controls (metronidazole, imipenem, meropenem, amoxicillin, amoxicillin-clavulanic acid, ticarcillin-clavulanic acid, cefotetan, cefoxitin and clindamycin) against 462 anaerobic bacterial strains. The reference agar dilution method was used according to the NCCLS standard. Faropenem demonstrated high antimicrobial activity, similar to that of both imipenem and meropenem (faropenem Minimal Inhibitory Concentrations 50% and 90% were 0.12 and 1 mg/L for all Gram-negative anaerobes, 0.25 and 1 mg/L for all Gram-positive anaerobes). Only 5 strains of the Bacteroides fragilis group (1.1% of all anaerobes) were resistant to faropenem, which compared favorably with that of other reference antianaerobic drugs. The results obtained confirm those previously reported.     

In vitro activity of ABT-492 against anaerobic bacteria

The purpose of the study was to determine the in vitro activity of ABT-492 compared with that of other antimicrobial agents against anaerobic bacteria. The activity of ABT-492 was investigated against 369 clinical isolates of anaerobic bacteria by the agar dilution method and was compared with that of moxifloxacin, piperacillin, cefoxitin, imipenem, clindamycin and metronidazole. ABT-492 and imipenem were the most active antimicrobial agents tested.     

In vitro activity of LY 333328 against anaerobic gram-positive bacteria.

LY 333328 is a new semisynthetic glycopeptide with reported activity against aerobic Gram-positive cocci such as enterococci, pneumococci, streptococci and staphylococci. The present investigation was undertaken to determine the in vitro activity of LY 333328 against 178 Gram-positive anaerobic bacteria recently isolated from human infections. The activity was compared with that of vancomycin, teicoplanin, cefoxitin, imipenem, clindamycin and metronidazole. Peptostreptococci (48 strains): LY 333328, range 0.016-1.0 mg/l; vancomycin, 0.125-2.0 mg/l; teicoplanin, 0.032-2.0 mg/l; cefoxitin, 0.064-8.0 mg/l; imipenem, 0.016-0.064 mg/l; clindamycin, 0.016-1.0 mg/l; metronidazole, 0.125-8.0 mg/l. Propionibacterium acnes (31 strains): LY 333328, range 0.032-0.125 mg/l; vancomycin, 0.25-0.5 mg/l; teicoplanin, 0.25-0.5 mg/l; cefoxitin, 0.125-1.0 mg/l; imipenem, 0.032-0.064 mg/l; clindamycin, 0.016-0.064 mg/l; metronidazole, 32-> or =64 mg/l. Clostridium difficile (50 strains): LY 333328, range 0.016-2.0 mg/l; vancomycin, 0.5-4.0 mg/l; teicoplanin, 0.064-0.5 mg/l; cefoxitin, 64-128 mg/l; imipenem, 8.0 mg/l; clindamycin, 0.25-128 mg/l; metronidazole, 0.125-0.25 mg/l. Clostridium perfringens (49 strains): LY 333328, range 0.016-2.0 mg/l; vancomycin, 0.025-4.0 mg/l; teicoplanin, 0.064-4.0 mg/l; cefoxitin, 0.5-1.0 mg/l; imipenem, 0.016-0.5 mg/l; clindamycin, 0.008-1.0 mg/l; metronidazole, 1.0-4.0 mg/l. LY 333328 had an excellent in vitro activity against anaerobic Gram-positive bacteria.     

In vitro activity of telithromycin, quinupristin/dalfopristin, linezolid and comparator antimicrobial agents against Staphylococcus aureus clinical isolates

We have studied the prevalence of the different macrolide, lincosamide, streptograminB (MLS(B)) phenotypes among clinical Staphylococcus aureus isolates erythromycin- and/or oxacillin-resistant; and also the activity of other antimicrobial agents including telithromycin, quinupristin/dalfopristin, linezolid, aminoglycosides, chloramphenicol and vancomycin. We found that 64.86% of S. aureus were oxacillin-resistant. While the most prevalent MLS(B) phenotype among methicillin-resistant S. aureus (MRSA) was constitutive MLS(B) (cMLS) (83%), among methicillin-susceptible S. aureus (MSSA) it was inducible MLS(B) (iMLS(B)) (90%). Kanamycin resistance was more frequent than resistance to other aminoglycosides, being 100% for MRSA. Telithromycin was only active against iMLS(B), MS and erythromycin-susceptible isolates, although resistance rates were found among iMLS(B) MSSA (2.78%). Quinupristin/dalfopristin showed greater activity, with resistance rates of 2.5% for MRSA and 1.53% for MSSA. Both vancomycin and linezolid were fully active against all the isolates tested, with the highest MIC value being 2 microg/ml and 4 microg/ml, respectively. Among MRSA strains, 81.67% displayed resistance to five or more antimicrobials. This multiresistance was more frequently found among cMLS(B) strains (96.38% MRSA resistant to 6-9 agents).     

Comparative in-vitro activity of fourteen antibiotics against clinical isolates of enterococci

The in-vitro 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 micrograms/ml, followed by penicillin G and piperacillin with MIC90 of 4 micrograms/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 enterococcal infections are discussed in the text.     

Comparative bactericidal activity of fluoroquinolones against clinical isolates resistant to fluoroquinolones

The bactericidal activity of levofloxacin, ciprofloxacin, moxifloxacin and norfloxacin against clinical isolates conventionally classified as resistant to fluoroquinolones were compared at their maximum concentrations in serum, urine (except moxifloxacin) and bronchial mucosa (except norfloxacin). Time killing curves against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Streptococcus pneumoniae were performed. Serum concentrations of the tested drugs were not able to produce a bactericidal effect on fluoroquinolone-resistant strains. In the urine series, levofloxacin was always bactericidal (decrease > or = 3 logs CFU/ml), while norfloxacin and ciprofloxacin were bactericidal on E. coli (both), P. mirabilis (norfloxacin) and P. aeruginosa (ciprofloxacin). In the bronchial mucosa series, S. pneumoniae was rapidly killed by levofloxacin and moxifloxacin, and K. pneumoniae by levofloxacin after 12 hours. In conclusion, the maximum levofloxacin concentrations achievable at certain body sites allowed killing even of strains defined as resistant by conventional breakpoints.     

In vitro activity of nitroxoline against clinical isolates of Candida species

The in vitro antifungal activity of the quinoline nitroxoline has been compared with those of amphotericin B, flucytosine, and two azoles, miconazole and ketoconazole, against clinical isolates of Candida spp. A total of 186 isolates of 10 species of Candida and two culture collection strains were tested by an agar-dilution technique. Nitroxoline was highly active against Candida spp. MICs for nitroxoline ranged between 0.25-2 micrograms ml-1 for 186 representative strains. With MIC90 as the measure of antifungal activity, nitroxoline appeared to be superior to the imidazoles studied. Data for individual species of Candida revealed that the activities of nitroxoline and amphotericin B were generally just as effective against C. albicans, whereas flucytosine was the most active agent against Candida spp.     

In vitro antifungal activity of sertaconazole against 309 dermatophyte clinical isolates

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 degrees C vs 35 degrees 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 microg/ml with a MIC range of 0.01-8 microg/ml. MIC50 and MIC90 were respectively of 0.25 and 1 microg/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 microg/ml respectively). Microsporum audouinii had the lowest susceptibility in the study (geometric mean 0.59 microg/ml). Considering MIC50 and MIC90 these differences were significantly in favor of the activity of sertaconazole against E. floccosum (0.06 and 0.5 microg/ml respectively).     

In vitro activity of fluconazole, voriconazole and caspofungin against clinical yeast isolates

Predicting the clinical outcome of a systemic mycosis is often a difficult task, especially when microbiological resistance is one of the factors contributing to therapeutic failure. Some of these factors are host-related--e.g. immune state, site and severity of infection, poor compliance to therapy--while others are associated with the drug's characteristics--e.g. dosage, type of compound (fungistatic/fungicidal), pharmacokinetic properties and drug-drug interactions. In the last few years, clinicians have been confronted with the problem of selecting the most appropriate antifungal therapy for systemic infections and have highlighted the need for a reliable method to assay the in vitro susceptibility of yeasts and molds to different antifungal agents, which would allow them to institute a tailored therapy. Using the CLSI micromethod--the reference method for clinically relevant yeast testing--we assayed 70 clinical yeast isolates ( Candida spp., collected from patients with systemic mycosis) for susceptibility against fluconazole, voriconazole and caspofungin. Data obtained from our in vitro susceptibility assays revealed good activity of azoles against the majority of Candida spp. In particular, 88.6% of the assayed isolates were susceptible to fluconazole, with minimum inhibitory concentrations (MICs) ranging from =0.125 microg/mL to 8 microg/mL; 97.1% of the isolates were susceptible to voriconazole, with MICs ranging from 0.008 microg/mL to 1 microg/mL; regarding caspofungin 72.9% of the isolates had MICs ranging from 0.25 microg/mL to 1 microg/mL.     

Antimicrobial activity of artemisinin and its derivatives against anaerobic bacteria

Artemisinin and nine of its semisynthetic derivatives were tested for antibacterial activity against anaerobic, facultative anaerobic, microaerophilic and aerobic bacteria. Only anaerobic bacteria and gonococci showed sensitivity to artemisinin derivatives. Artemisinin and its deoxy derivatives had no activity at 100 micrograms/ml concentration. The newly synthesized methyl diperoxy derivative had the highest activity against all tested anaerobes with a MIC of 9.4 micrograms/ml.     

In vitro bactericidal activity of antibiotic combinations against clinical isolates of Mycobacterium chelonae

Mycobacterium chelonae is one of the most antibiotic-resistant species of the pathogenic, rapidly-growing mycobacteria. The objective of this study was to evaluate the bactericidal activity of classical and new potential drugs, alone and in combinations, against clinical isolates of Mycobacterium chelonae. Clarithromycin was seen to be the most bactericidal drug. In drug combinations, this compound is most useful with gentamicin, fluoroquinolones, rifampicin, linezolid, other aminoglycosides, doxycyline and carbapenems. The combination of tobramycin with ciprofloxacin or moxifloxacin also exhibits similar activity. In conclusion, this study on bactericidal activity of drug combinations against Mycobacterium chelonae confirms the utility of clarithromycin associated with other drugs, and, of the new drugs, the value of moxifloxacin and linezolid.     

In vitro activity of ertapenem against common clinical isolates in relation to human pharmacokinetics

The in vitro activity of ertapenem against bacterial pathogens isolated from patients with moderate to severe complicated intra-abdominal, complicated skin/skin structure, acute pelvic, or complicated urinary tract infection or community acquired pneumonia was compared to ceftriaxone and piperacillin-tazobactam and related to known plasma concentrations of the three agents. Ertapenem was more potent against methicillin-susceptible Staphylococcus aureus (MSSA) than ceftriaxone and piperacillin-tazobactam and was more potent and more active than both of these agents against Enterobacteriaceae and anaerobes. Piperacillin-tazobactam was the most active agent against enterococci and Pseudomonas aeruginosa. All isolates of Enterobacteriaceae (n=1088), Streptococcus pyogenes (n=37), Streptococcus agalactiae (n=48), MSSA (n=187), Haemophilus influenzae (n=59), and Moraxella catarrhalis (n=9) were susceptible to ertapenem; < 1% of 1284 anaerobes and only 1 of 113 Streptococcus pneumoniae (a penicillin-resistant isolate) were resistant to ertapenem. The MIC value at which 90% of all Enterobacteriaceae, streptococci, MSSA, H. influenzae, M. catarrhalis, and anaerobes were inhibited (MIC90) was < or = 1 microg/ml and below the mean plasma concentration of total ertapenem following a 1 g intravenous infusion for at least 24 hours, i.e., the entire recommended dosing interval, and below the free drug concentration for at least 8 h.     

Comparative in vitro activity of sparfloxacin (AT 4140, RP 64206--SPFX) against 275 multiresistant clinical isolates.

The in-vitro activity of sparfloxacin was compared with that of pefloxacin, ofloxacin, ciprofloxacin, imipenem, ceftazidime, gentamicin and amikacin against 275 multiresistant nosocomial clinical isolates. They consisted of Pseudomonas aeruginosa (37), Enterobacter cloacae (42), Acinetobacter anitratus (60), Klebsiella pneumoniae (37) and Staphylococcus sp (99). Minimum inhibitory concentrations (MIC90) and geometric mean MICs for sparfloxacin were as follows (mg/l): P. aeruginosa 128-23.7, E. cloacae 1-0.13, A. anitratus 2-0.14, K. pneumoniae 1-0.08, MRSA 16-0.98, MSSA 0.12-0.03, MRSE 0.25-0.12 and MSSE 0.12-0.05. It is concluded that sparfloxacin was the most potent agent against staphylococci and A. anitratus including strains resistant to the other quinolones while ciprofloxacin was the most potent agent against P. aeruginosa, E. cloacae and K. pneumoniae.     

In vitro activity of ceftazidime/avibactam against clinical isolates of ESBL-producing Enterobacteriaceae in Italy

Resistance to carbapenems in Enterobacteriaceae is a serious concern for public health. Alternative treatment options involving carbapenem-sparing regimen for patients with serious infections caused by multidrug-resistant Enterobacteriaceae are urgently needed. Ceftazidime/avibactam (CZA) is a new combination of a third generation cephalosporin and a non-β-lactam β-lactamase inhibitor, in which avibactam is capable to expand the ceftazidime activity also against extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. To date, no data exist regarding the activity of CZA against strains isolated in the Italian context, which is known as endemic for ESBL producers. The aim of this study was to evaluate the in vitro activity of CZA, in comparison to ceftazidime (CAZ), against 90 ESBL-producing Escherichia coli and Klebsiella pneumoniae isolates, collected from blood and urine samples at our Institute. Thus, avibactam has been able to restore the activity of CAZ in all cases, suggesting the potential use of CZA as a carbapenem-sparing model, especially when limited therapeutic options exist.     

In vitro activity of daptomycin alone and in combination with various antimicrobials against Gram-positive cocci

The increasing prevalence of resistant Gram-positive cocci requires the need to search for more effective agents and synergistic combinations. Forty-two vancomycin-resistant Enterococcus faecium (VREF), 30 methicillin-resistant Staphylococcus aureus (MRSA) and 36 Staphylococcus epidermidis (MRSE) strains were studied. Minimum inhibitory concentrations (MICs) were determined and synergy testing was performed by using E test for daptomycin, ampicillin-sulbactam, piperacillin-tazobactam and ticarcillin-clavulanate against staphylococci; for daptomycin, ampicillin, rifampin, and gentamicin against enterococci. Daptomycin in combination with ampicillin, rifampin, and gentamicin was tested against enterococci; daptomycin in combination with ampicillin-sulbactam, piperacillin-tazobactam, and ticarcillin-clavulanate was tested against staphylococci. Interaction categories were defined by the fractional inhibitory concentration (FIC) index. All strains of staphylococci and enterococci were susceptible to daptomycin. All three combinations showed synergy against more than 70% of the MRSA strains. Daptomycin in combination with ampicillin, rifampin, and gentamicin against enterococci showed synergies of 64.2%, 57.1% and 21.4%, respectively. This study indicates that daptomycin alone and combined with beta-lactams seems to be effective against MRSA, but further in vitro and in vivo studies on the subject are required before clinical use can be recommended.     

Comparison of in vitro exemestane activity versus other antiaromatase agents

Anastrozole, letrozole, and exemestane are the most selective and potent oral antiaromatase agents currently available. However, in vitro and in vivo studies comparing these agents are lacking. Anastrozole and letrozole are reversible, competitive nonsteroidal type II inhibitors, whereas exemestane is an irreversible steroidal type I inactivator. The study was conducted to determine the impact of this characteristic on in vitro residual aromatase activity and protein levels after incubation of JEG-3 cells with aminoglutethimide (a type II inhibitor), anastrozole, exemestane, or letrozole. Aromatase activity was measured after various incubation times with each antiaromatase agent at a concentration 10 times higher than IC50 (concentration giving 50% inhibition). Only exemestane induced a residual inhibition of aromatase activity after its removal, without any change in the aromatase protein level. Aromatase activity increased after preincubation of JEG-3 cells with either aminoglutethimide or anastrozole without any change in the aromatase protein level. The aromatase protein level increased rapidly when cells were incubated with letrozole and aromatase activity inhibition disappeared immediately after removal of the drug. The breakthrough effects in aromatase activity or protein levels observed after treatment with reversible inhibitors may be a factor in therapeutic failure with these agents. These results suggest a possible advantage for exemestane because it is the only clinically available oral irreversible aromatase inactivator.