Comparative activity of linezolid against staphylococci and enterococci isolated in Italy

The activity of linezolid, a new oxazolidinone, was tested against 862 Gram-positive cocci isolated in Italy and compared with the activities of 12 antibiotics. Overall, MIC₉₀s for linezolid (2–4 mg/L) indicated an in vitro activity comparable to that of vancomycin in methicillin-resistant Staphylococcus aureus (4 mg/L), S. epidermidis (2 mg/L) and methicillin-susceptible strains. Enterococcus faecalis strains were susceptible to linezolid (MIC₉₀ 2–4 mg/L), glycopeptides and β -lactams. In E. faecium , only glycopeptides (MIC₉₀ 2 mg/L) and linezolid (MIC₉₀ 2 mg/L) were active. Linezolid was the only drug active against two strains of Enterococcus showing a VanA phenotype. Owing to its antibacterial profile, linezolid represents a promising drug for the treatment of Gram-positive infections.     

In vitro activity of tigecycline and occurrence of tetracycline resistance determinants in isolates from patients enrolled in phase 3 clinical trials for community-acquired pneumonia

The in vitro activity of tigecycline was evaluated against baseline pathogens isolated from patients enrolled in phase 3 clinical trials for community-acquired pneumonia conducted in 29 countries worldwide. Tigecycline was active against the most prevalent pathogens, including Streptococcus pneumoniae (MIC₉₀ 0.06 mg/L), Staphylococcus aureus (MIC₉₀ 0.25 mg/L), Haemophilus influenzae (MIC₉₀ 0.5 mg/L) and Klebsiella pneumoniae (MIC₉₀ 1 mg/L). Twelve isolates of S. pneumoniae expressing tet (M) and two isolates of K. pneumoniae producing extended-spectrum β-lactamases isolated during the study were susceptible to tigecycline. The excellent in vitro activity of tigecycline against these clinical isolates confirmed its potential utility against pathogens associated with community-acquired pneumonia.     

Antimicrobial activity against strains of Escherichia coli and Klebsiella spp. with resistance phenotypes consistent with an extended-spectrum β-lactamase in Europe

Extended-spectrum β-lactamases (ESBLs) have continued to evolve after their initial detection in Europe nearly two decades ago. The summary results from the MYSTIC Program (31 medical centers) were utilized to assess the extent of ESBL occurrence in Europe from 1997 to 2000. ESBL phenotype rates in Klebsiella spp. (32.8%) and Escherichia coli (14.4%) were generally stable, but extensive hospital-to-hospital and unit-to-unit variations were noted. The highest ESBL rates were found in eastern Europe (including Turkey) and in intensive care unit patient populations. Carbapenems remained active against the ESBL-producing strains (meropenem MIC₉₀, 0.25–1 mg/L), while some other agents, such as aminoglycosides, fluoroquinolones, and piperacillin–tazobactam, were significantly less effective. International surveillance initiatives should be maintained to monitor future progression of this important resistance.     

In vitro activities of new quinolones against Brucella melitensis isolated in a tertiary-care hospital in Turkey

We have evaluated the in vitro activities of seven fluoroquinolones against 69 strains of Brucella melitensis . According to their minimum inhibitory concentration for 90% growth (MIC₉₀) values, the most active agent was found to be sparfloxacin (MIC₉₀ 0.12 mg/L) followed by levofloxacin, ciprofloxacin, ofloxacin (MIC₉₀ 0.50 mg/L) and grepafloxacin (MIC₉₀ 1 mg/L), gemifloxacin (MIC₉₀ 2 mg/L) and gatifloxacin (MIC₉₀ 4 mg/L).     

Activity of telithromycin against 26 quinolone-resistant pneumococci with known quinolone-resistance mechanisms

NCCLS agar dilution was used to test activity of telithromycin compared to clarithromycin, penicillin G, ciprofloxacin, levofloxacin, sparfloxacin and moxifloxacin against 26 pneumococci with defined quinolone resistance (type II topoisomerase and efflux) mechanisms. Thirteen strains were penicillin susceptible, six intermediate and seven resistant. Clarithromycin resistance ( mef and/or erm ) was seen in eight strains. Ciprofloxacin MICs (mg/L) were 8–64 compared to 1–32 (levofloxacin), 0.5 ≥ 32 (sparfloxacin) and 0.125–4 (moxifloxacin). Telithromycin MIC₅₀ and MIC₉₀ values (mg/L) were 0.016 and 0.25, with only one strain having an MIC of 2 mg/L.     

Antimicrobial susceptibility of anaerobic bacteria in Belgium as determined by E-test methodology

The objective was to collect recent data on the antibiotic susceptibility of clinically significant anaerobes in Belgium. A total of 333 anaerobic clinical isolates from various body sites were prospectively collected between 2005 and 2007 at two tertiary care hospitals in Belgium. The minimal inhibitory concentrations (MICs) were determined using the E-test method for nine anti-anaerobic antibiotics. Sixty-one percent of the isolates were β-lactamase producers, which explains the poor activity of penicillin. Amoxicillin/clavulanic acid, piperacillin/tazobactam, metronidazole and meropenem were very active against most anaerobes, but around 10% of the Bacteroides fragilis group strains were non-susceptible to the two β-lactam/β-lactamase inhibitors. No resistance was observed to metronidazole, while 3% of the Bacteroides spp. had decreased susceptibility to meropenem (MIC ≥ 4 mg/L). Cefoxitin, clindamycin and moxifloxacin were less active, with 33%, 52% and 57% of the B. fragilis group being non-susceptible respectively. Tigecycline showed consistently good activity against most anaerobes with MIC₅₀ and MIC₉₀ of 0.25 and 2 mg/L. Metronidazole, amoxicillin/clavulanate, piperacillin/tazobactam and meropenem remain good empirical choices when anaerobes are expected in our setting. Because of the occurrence of resistance to most classes of current anti-anaerobic antibiotics, it is recommended that the antimicrobial resistance patterns be monitored regularly in order to guide empirical therapy.     

Antibacterial effects of Eucalyptus globulus leaf extract on pathogenic bacteria isolated from specimens of patients with respiratory tract disorders

The antibacterial activity of Eucalyptus globulus leaf extract was determined for 56 isolates of Staphylococcus aureus , 25 isolates of Streptococcus pyogenes , 12 isolates of Streptococcus pneumoniae and seven isolates of Haemophilus influenzae obtained from 200 clinical specimens of patients with respiratory tract disorders. MIC₅₀s for these species were 64, 32, 16 and 16 mg/L, respectively; MIC₉₀s were 128, 64, 32 and 32 mg/L, respectively; and MBC s were 512, 128, 64 and 64 mg/L, respectively. These results suggest that further studies to clarify the possible therapeutic role of E. globulus leaf extract in the treatment of respiratory tract infection are warranted.     

CQ-397 and CQ-414: antimicrobial activity and spectrum of two fluoroquinolone–cephalosporin, dual-action compounds with carboxamido bonds

Objective: To evaluate the potential spectrum of activity of two novel dual-action compounds with carboxamido bonds (CQ-397 and CQ-414; Laboratories Aranda, San Rafael, Mexico) against human pathogens.
Method: Approximately 800 Gram-positive and Gram-negative aerobic clinical bacteria were tested in vitro using the Mueller-Hinton broth microdilution method of the National Committee of Clinical Laboratory Standards.
Results: CQ-397 (cefamandole+enrofloxacin) and CQ-414 (cefamandole+norfloxacin) were equally potent against Enterobacteriaceae (MIC₉₀ range, 0.06–0.5 μg/mL and 0.06-1 μg/mL, respectively). Citrobacter freundii (MIC₉₀, 4 μg/mL) and Providencia spp. (MIC₉₀,>32 μg/mL) exhibited elevated study drug MICs. Enterobacteriaceae resistant to fluoroquinolones generally remained resistant. CQ-397 and CQ-414 were active against Stenotrophomonas maltophilia (MIC₉₀, 4 μg/mL) and oxacillin-susceptible staphylococci (MIC₉₀, 0.25 μg/mL), but not oxacillin-resistant Staphylococcus aureus (MIC₉₀,>32 μg/mL), Staphylococcus epidermidis (MIC₉₀, 8 μg/mL), and enterococci (MIC₉₀s, 8 to>32 μg/mL). There was no difference in the dual-action drug activity (MIC₉₀, 2 μg/mL) between penicillin-susceptible and -resistant pneumococci. Haemophilus influenzae and Moraxella catarrhalis were very susceptible (MIC range, <0.015-0.06 μg/mL) to both compounds.
Conclusions: The activity of these novel dual-action compounds, formed from the bonding of older antimicrobials, warrants further investigation for potential human and/or animal health use, including toxicology and pharmacokinetics.     

Antimicrobial susceptibility of 840 clinical isolates of Haemophilus influenzae collected in four European countries in 2000–2001

In 2000–2001, 840 clinical isolates of Haemophilus influenzae were collected from laboratories in France, Germany, Italy and Spain (210 isolates/country). β -Lactamase production among the isolates varied considerably by country, ranging from 8.1% in Germany to 34.8% in France. H. influenzae from patients ≤4 years old showed the highest prevalence of β -lactamase production (23.2%), compared with isolates from patients aged 5–17 years (17.8%) and ≥18 years (16.5%). All isolates were susceptible to amoxicillin–clavulanate, ciprofloxacin and levofloxacin; 99.6% and 98.9% of isolates were susceptible to azithromycin and cefuroxime, respectively. Among the macrolides tested, azithromycin (MIC₉₀, 2 mg/L) was eight-fold more potent than clarithromycin (MIC₉₀, 16 mg/L) and roxithromycin (MIC₉₀, 16 mg/L). Despite variations in β -lactamase production between different countries, > 99% of all isolates were susceptible to amoxicillin–clavulanate, ciprofloxacin, levofloxacin, and azithromycin.     

Antimicrobial activity of LB10827, a new orally administered cephalosporin, tested against Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae

A new orally administered cephalosporin, LB10827, was compared to 16 other antimicrobial agents tested against Streptococcus pneumoniae (520 strains), Haemophilus influenzae (302 strains) and Moraxella catarrhalis (188 strains) by reference broth microdilution methods. LB10827 (MIC₉₀, 0.12 mg/L; highest MIC, 0.5 mg/L) was 8–16-fold more potent than cefdinir, cefpodoxime or cefuroxime when tested against S. pneumoniae . All Gram-negative strains were inhibited at ≤ 0.5 mg/L LB10827, which is an activity equal or superior to that of currently available and tested oral β-lactams. LB10827 appears to be a promising agent worthy of continued investigations both in vitro and in vivo.     

Antimicrobial Activity of SCH 27899, Oligosaccharide Member of the Everninomycin Class with a Wide Gram-Positive Spectrum

The in vitro antimicrobial activity of SCH 27899 (everninomycin), a novel oligosaccharide compound of the everninomycin class, was compared with vancomycin, chloramphenicol, clinafloxacin, teicoplanin and doxycycline against 428 clinical strains of bacteria. Everninomycin base exhibited the greatest antimicrobial activity compared to other formulations against all strains tested (MIC₉₀: 0.25 μ/ml) followed by clinafloxacin and teicoplanin (MIC₉₀: 0.5 μg/ml), vancomycin (MIC₉₀: 2 μg/ml), and doxycycline (MIC₉₀: 16 μg/ml). Everninomycin demonstrated the best activity against Streptococcus spp. (serogroups A, B, C, F, G) and Streptococcus pneumoniae , and lower activity against coagulase-negative staphylococci (MIC₉₀: 0.5 μg/ml). All enterococci had an everninomycin MIC of 0.5 μg/ml or less. Everninomycin had no measurable antimicrobial activity against gram-negative aerobic organisms except Flavo-bacterium meningosepticum (MIC₅₀: 2 μg/ml). Some everninomycin activity was observed against Clostridium spp., Peptostreptococcus spp., and the Prevotella bivius-disiens group. Everninomycin showed excellent activity (MIC₉₀: 0.25 μg/ml) against the fluoroquinolone-resistant strains and all gram-positive strains resistant to vancomycin (MICs 4 μg/ml). The MBC/MIC ratios and killing curve data suggest that everninomycin is not uniformly or rapidly bactericidal. These in vitro data indicate that everninomycin could be useful against emerging gram-positive strains resistant to other contemporary antimicrobials.     

In vitro activity of gatifloxacin, a new fluoroquinolone, against 204 anaerobes compared to seven other compounds

The activity of gatifloxacin, a new fluoroquinolone derivative, was compared with the activities of ciprofloxacin, levofloxacin, amoxicillin, amoxicillin–clavulanate, imipenem, clindamycin and metronidazole against 204 anaerobes isolated from clinical specimens, by MIC determination, using the reference agar dilution method. When determining the overall activity against anaerobes, the MIC_50/90 (mg/L) values were amoxicillin 16/>64, amoxicillin–clavulanate 0.125/1, imipenem 0.25/0.5, clindamycin 0.5/>256, metronidazole 1/8, ciprofloxacin 2/32, levofloxacin 1/8 and gatifloxacin 0.5/4. The broad in vitro spectrum of gatifloxacin is promising for the treatment of mixed anaerobic infections, especially those of the respiratory tract, ear, sinus, skin and soft tissues, and bite wounds. These data suggest that gatifloxacin may have a clinical role in the treatment of infections in which anaerobic pathogens are involved.     

Prevalence of erm methylase genes in clinical isolates of non-pigmented, rapidly growing mycobacteria

The aim of this study was to determine the frequency of erm genes coding for macrolide resistance among clinical isolates of non-pigmented rapidly growing mycobacteria (NPRGM) and to evaluate their importance in phenotypic resistance. Broth microdilution susceptibility testing was performed for all NPRGM tested. A PCR assay with consensus primers was used to evaluate the presence of erm genes among the 167 clinical isolates studied, which belonged to nine species of NPRGM; erm genes were detected in all nine species and 109 strains were erm -positive. The highest percentage of erm -positive isolates was found among Mycobacterium mageritense (100%) and the lowest among Mycobacterium mucogenicum (14%). The MICs of macrolides were found to be lower for erm -negative isolates (MIC₉₀: 2 mg/L) than for erm- positive isolates (MIC₉₀: 16 mg/L), although in some cases high MICs were found for erm -negative isolates. The finding that erm methylases are present in the majority of the species of NPRGM analysed in this study is not in agreement with conventional susceptibility studies. It therefore appears necessary to use a combination therapy to treat infections caused by NPRGM.     

In vitro activity of levofloxacin against contemporary clinical isolates of Legionella pneumophila, Mycoplasma pneumoniae and Chlamydia pneumoniae from North America and Europe

Objective   To assess the activities of levofloxacin and the comparator agents erythromycin, clarithromycin, azithromycin and doxycycline against atypical respiratory pathogens.
Methods   One hundred and forty-six Legionella pneumophila , 41 Mycoplasma pneumoniae and nine Chlamydia pneumoniae isolates were procured from various culture collections in North America and Europe and tested for susceptibility to the above agents by broth microdilution. The isolates came primarily from clinical sources and were collected from patients between 1995 and 1999.
Results   Against L. pneumophila , levofloxacin was the most active agent, with an MIC₉₀ of 0.03 mg/L, twofold more active than clarithromycin (0.06 mg/L), 16-fold more active than erythromycin and azithromycin (0.5 mg/L) and 64-fold more active than doxycycline. Against M. pneumoniae , azithromycin (MIC₉₀ ≤ 0.0005 mg/L) was the most active agent. However, two isolates of M. pneumoniae , one from the USA and one from Finland, were macrolide resistant (MIC ≥ 4 mg/L), but levofloxacin susceptible (MIC 0.25 mg/L). The geographic origin of L. pneumophila and M. pneumoniae did not affect the MIC range for any antimicrobial agent tested. Against C. pneumoniae , clarithromycin was the most active agent, with an MIC range of ≤0.008–0.03 mg/L.
Conclusions   Levofloxacin had comparable activity to the other agents tested against the atypical respiratory pathogens, confirming its potential as an alternative for empirical therapy of community-acquired pneumonia.     

In vitro activity of ceftriaxone combined with tazobactam against anaerobic bacteria

The in vitro activity of ceftriaxone combined with tazobactam against 190 strains of anaerobic bacteria was compared with that of amoxicillin with clavulanic acid, ampicillin with sulbactam, piperacillin alone and with tazobactam, cefoxitin, and imipenem, i.e. beta-lactam antibiotics established in the treatment of anaerobic infections. All anaerobes tested were susceptible to 32 mg/l ceftriaxone when tazobactam was added at fixed ratios (ceftriaxone to tazobactam) of 2:1 and 8:1 and at constant concentrations of 2,4 and 8 mg/l, respectively. When 4 mg/l tazobactam was added, the MICs of ceftriaxone for 83 of 94 strains of theBacteroides fragilis group were reduced by a factor of 8 to 512; for eight strains, this reduction was two to fourfold. Only the MICs of ceftriaxone for threeBacteroides fragilis strains were not influenced.     

Highly antibiotic-resistant Acinetobacter baumannii clinical isolates are killed by the green tea polyphenol (–)-epigallocatechin-3-gallate (EGCG)

Acinetobacter baumannii is an increasingly common cause of infection in intensive-care units throughout the world, and the occurrence of multiresistant A. baumannii is increasing. The aim of this study was to determine whether a highly purified polyphenol, (–)-epigallocatechin-3-gallate (EGCG), from green tea ( Camellia sinesis ), had antimicrobial effects against multiresistant clinical isolates of A. baumannii. Standard microplate assays were performed to determine the MIC of EGCG for 21 clinical isolates of A. baumannii. MICs ranged from 0.078 to 0.625 mg/mL, with MIC₅₀ and MIC₉₀ of 0.312 mg/mL and 0.625 mg/mL, respectively. All of the isolates of A. baumannii tested were killed by EGCG. In time-kill assays, EGCG resulted in a 3-log reduction in CFU/mL of A. baumannii after 5 h of incubation with the polyphenol. Synergy between the commonly used topical agent 5% mafenide acetate (Sulfamylon) and EGCG was noted for one clinical isolate, and partial synergy was noted for three other isolates. These findings demonstrate that EGCG is an effective bactericidal agent against antibiotic-resistant A. baumannii clinical strains in laboratory settings. EGCG has previously been shown to be safe, and therefore may be an attractive addition for the treatment of cutaneous A. baumannii infections where high concentrations of the drug can be applied to the wound surface.     

In vitro activity of evernimicin and selected antibiotics against methicillin-resistant staphylococci: a 24-country study

Objective   To collect and analyze data on susceptibility of methicillin-resistant staphylococci to evernimicin and other antimicrobial agents.
Methods   Recent clinical isolates of methicillin-resistant staphylococci from 33 laboratories in North America, Europe and South Africa were investigated.
Results   Of the antimicrobial agents tested, evernimicin had the lowest MIC₉₀s for methicillin-resistant Staphylococcus aureus and methicillin-resistant coagulase-negative staphylococci (0.75 and 1.0 mg/L, respectively). Resistance to ciprofloxacin and erythromycin was widespread, with higher levels of resistance in North America than in other regions.
Conclusions   Susceptibility surveys help to determine the antimicrobial activity of new agents. Ciprofloxacin- and erythromycin-resistant staphylococci were prevalent throughout all regions.     

Comparative in vitro activities of five quinolone antibiotics, including gemifloxacin, against clinical isolates

The in vitro activities of ciprofloxacin, ofloxacin, norfloxacin, levofloxacin and gemifloxacin against 343 clinical isolates were compared. Gemifloxacin showed the greatest activity, with MIC₉₀ values as low as 0.03–0.25 mg/L against Streptococcus pneumoniae , Haemophilus influenzae , Moraxella catarrhalis , methicillin-susceptible Staphylococcus aureus and Klebsiella pneumoniae , while methicillin-resistant Staphylococcus aureus , Enterococcus spp., Pseudomonas spp., Acinetobacter spp., Escherichia coli and Enterobacter spp. strains exhibited low rates of susceptibility to all five fluoroquinolones.     

Susceptibility of strains of Streptococcus agalactiae to macrolides and lincosamides, phenotype patterns and resistance genes

The Group B streptococcus ( Streptococcus agalactiae ) is a pathogen of increasing importance in human disease. We therefore studied the susceptibility of clinical isolates of S. agalactiae to penicillin G, erythromycin, azithromycin and clindamycin using National Committee for Clinical Laboratory Standards methodology, and we also determined the phenotypes of macrolide-lincosamide susceptibility and the resistance genes implicated in a group of selected isolates of the different phenotypes. We used 221 isolates collected between 1997 and 1999 in two Health Authority Areas in Móstoles and Granada, Spain. The minimal concentration for 90% inhibition (MIC₉₀) for penicillin G was 0.12 mg/L and all the isolates tested were susceptible. One hundred and eighty-five (83.7%) were susceptible to erythromycin and azithromycin and 191 (86.4%) were susceptible to miocamycin and clindamycin. Twenty-three isolates (10.4%) had a constitutive MLS_B phenotype, seven (3.2%) an inducible phenotype, and six (2.7%) an M phenotype. All except one of the MLS_B phenotype isolates tested ( n  = 23) carried erm genes; in two strains with the mef (A) gene, all the M phenotype ( n  = 6) isolates tested carried mef genes, while erm and mef (A) genes were absent in all the macrolide-lincosamide-susceptible ( n  = 12) isolates tested. In our environment, resistance to macrolide and lincosamide in S. agalactiae was present in 10–16% of the isolates. The majority of resistant strains had the MLS_B phenotype.     

Antimicrobial susceptibility of Bacteroides fragilis group isolates in Europe

Objective  To evaluate the activity of old and newer antianaerobic drugs against clinical isolates of Bacteroides fragilis group strains from different parts of Europe.
Methods  Bacteroides fragilis group isolates from 37 laboratories in 19 countries were biochemically characterized. The MICs of seven antimicrobial agents were determined by the agar dilution method as recommended by the NCCLS. Production of beta-lactamase was detected by nitrocefin.
Results  There were 1284 B. fragilis group isolates included in the study. Abdominal infections and wounds were the most common sources of isolation and B. fragilis was the dominating species. Ninety-nine percent of the strains were resistant to ampicillin (breakpoint 2 mg/L), 6% to cefoxitin (64 mg/L), 15% to clindamycin (8 mg/L) and 9% to moxifloxacin (8 mg/L). Less than 1% were resistant to imipenem (16 mg/L), piperacillin-tazobactam (128 mg/L) and metronidazole (32 mg/L). Ninety-six percent of the isolates were beta-lactamase producers.
Conclusions  Antimicrobial resistance among the B. fragilis group is increasing.