In vitro activity of trimethoprim againstBorrelia burgdorferi

A new culture medium has been developed to evaluate the activity of trimethoprim and sulfamethoxazole againstBorrelia burgdorferi in vitro. In this specially modified Barbour-Stoenner-Kelly medium, in which antagonizing substances were reduced to a minimum, trimethoprim was more active againstBorrelia burgdorferi than against a sensitive strain ofEscherichia coli, but sulfamethoxazole was not active againstBorrelia burgdorferi.     

Comparative antimicrobial activity of the new macrolide flurithromycin against respiratory pathogens

The activity of flurithromycin againstHaemophilus influenzae, Streptococcus pneumoniae, Streptococcus pyogenes, Branhamella catarrhalis andStaphylococcus aureus was determined by the agar dilution method. Flurithromycin showed high activity againstStreptococcus pneumoniae, Streptococcus pyogenes andBranhamella catarrhalis (MIC90=0.032–0.25 mg/l). Its MIC90 value againstHaemophilus influenzae strains was 4.0 mg/l and 16 mg/l againstStaphylococcus aureus strains. Flurithromycin has promising antibacterial activity which warrants clinical trials.     

Comparative in vitro activity of IY146032 (daptomycin), a new lipopeptide antimicrobial

The in vitro activity of LY146032, a new cyclic lipopeptide antibiotic, was compared with those of vancomycin, teicoplanin, and either oxacillin or ampicillin by determining agar dilution MIC values for 304 clinical gram-positive isolates. LY146032 had superior in vitro activity against oxacillin-resistant staphylococci when compared to vancomycin or teicoplanin. Against oxacillin-sensitive staphylococci, group JK-diphtheroids, streptococci,Listeria monocytogenes andClostridium difficile, LY146032 was equally or less active than vancomycin, teicoplanin, or the penicillins tested. When tested by macrobroth dilution MIC/MBC., LY 146032 showed good bactericidal activity against all organisms with the exception ofClostridium difficile.     

In vitro antimicrobial activity of the new antibiotic vermisporin

The antimicrobial activity of vermisporin, a new antibiotic produced by fermentation of the fungusOphiobolus vermisporis, was tested in vitro. Vermisporin inhibited 90 % ofBacteroides fragilis and otherBacteroides spp. at 1 µg/ml (range 0.25–1 µg/ml).Clostridium perfringens were inhibited by 1 µg/ml (range 0.25–2 µg/ml). Vermisporin inhibited 90 % ofStaphylococcus aureus, including methicillin-resistantStaphylococcus aureus, at 0.5 µg/ml (range 0.12–0.5 µg/ml). Vermisporin MICs for group A, B, C, F and G streptococci were < 1 µg/ml when tested in Haemophilus Test Medium but 8 µg/ml in the presence of blood. Vermisporin MICs forEnterobacteriaceae, Pseudomonas aeruginosa andHaemophilus influenzae exceeded 64 µg/ml. Inhibited organisms had MBCs 16- to 32-fold above the MICs.     

Comparative study on the macrolides erythromycin and clarithromycin: antibacterial activity and influence on immune responses

The in vitro activity of erythromycin and clarithromycin (a new macrolide antibiotic) on clinical bacterial isolates as well as their effects on the cellular and humoral immune responses in BALB/c-mice and on human granulocytes/monocytes was investigated. Treatment of BALB/c-mice for 7 days with these drugs did not influence the delayed type hypersensitivity to oxazolone nor the production of IgG and IgM immunoglobulins. In vitro, exposure of granulocytes to erythromycin resulted in increased phagocytosis only in higher concentrations (20 mcg/ml), whereas clarithromycin enhanced chemiluminescence response of granulocytes in concentrations ranging from 2.5-20 mcg/ml. Subinhibitory concentrations of both substances modified Staphylococcus aureus and made them more susceptible for granulocyte phagocytosis.     

Hemolytic activity of Borrelia burgdorferi.

Zones of beta-hemolysis occurred around colonies of Borrelia burgdorferi grown on Barbour-Stoenner-Kelly medium containing agarose and horse blood. Blood plates were inoculated with either the infective strain Sh-2-82 or noninfective strain B-31 in an overlay and incubated in a candle jar. Both strains of B. burgdorferi displayed beta-hemolysis after 1 to 2 weeks of incubation. The hemolytic activity diffused out from the borrelial colonies, eventually resulting in lysis of the entire blood plate. Hemolysis was most pronounced with horse blood and was less intense with bovine, sheep, and rabbit blood. Hemolysis was enhanced by hot-cold incubation, which is typical of phospholipase-like activities in other bacteria. Further characterization of the borrelial hemolysin by using a spectrophotometric assay revealed its presence in the supernatant fluids of stationary-phase cultures. Detection of the borrelial hemolytic activity was dependent on activation of the hemolysin by the reducing agent cysteine. This study provides the first evidence of hemolytic activity associated with B. burgdorferi.     

Activity of new macrolides againstBordetella pertussis andBordetella parapertussis

MICs and MBCs of four new macrolides (azithromycin, clarithromycin, dirithromycin and roxithromycin) and two older macrolides (erythromycin and josamycin) forBordetella pertussis andBordetella parapertussis were determined. The activity of the new macrolides was as good as that of erythromycin, while josamycin was slightly less active.Bordetella parapertussis was more resistant thanBordetella pertussis.     

Comparative in vitro antimicrobial activity of tigecycline, a new glycylcycline compound, in freshly prepared medium and quality control

The in vitro spectra of activity of tigecycline and tetracycline were determined for 2,490 bacterial isolates representing 50 different species or phenotypic groups. All isolates were tested simultaneously by broth microdilution using freshly prepared Mueller-Hinton broth and by disk diffusion. Portions of these data were submitted to the Food and Drug Administration (FDA) in support of the sponsor's application for new drug approval. In a separate study, MIC and disk diffusion quality control ranges were determined. The tigecycline MICs at which 50%/90% of bacteria were inhibited were (in microg/ml) as follows: for Streptococcus spp., 0.06/0.12; for Moraxella catarrhalis, 0.06/0.12; for Staphylococcus spp., 0.12/0.25; for Enterococcus spp., 0.12/0.25; for Listeria monocytogenes, 0.12/0.12; for Neisseria meningitidis, 0.12/0.25; for Haemophilus spp., 0.25/0.5; for Enterobacteriaceae, 0.05/2.0; for non-Enterobacteriaceae, 0.5/8.0. Tigecycline was consistently more potent than tetracycline against all species studied. The data from this study confirm the FDA-approved MIC and disk diffusion breakpoints for tigecycline for Streptococcus spp. other than Streptococcus pneumoniae, enterococci, and Enterobacteriaceae. Provisional breakpoints for Haemophilus spp. and S. pneumoniae are proposed based on the data from this study. The following MIC and/or disk diffusion quality control ranges are proposed: Staphylococcus aureus ATCC 29213, 0.03 to 0.25 microg/ml; S. aureus ATCC 25923, 20 to 25 mm; Escherichia coli ATCC 25922, 0.03 to 0.25 microg/ml and 20 to 27 mm; Pseudomonas aeruginosa ATCC 27853, 9 to 13 mm, Enterococcus faecalis ATCC 29212, 0.03 to 0.12 microg/ml; S. pneumoniae ATCC 49619, 0.015 to 0.12 microg/ml and 23 to 29 mm; Haemophilus influenzae ATCC 49247, 0.06 to 0.5 microg/ml and 23 to 31 mm; and Neisseria gonorrhoeae ATCC 49226, 30 to 40 mm.     

Comparative in vitro activity of the new fluoroquinolone BMY-40062

The results are presented of comparative in vitro susceptibility testing of BMY-40062, a new fluorinated quinolone which contains a tetrabutyl moiety at N-1 and a piperazinyl group at C-7. BMY-40062 inhibited 90 % ofEnterobacteriaceae strains at < 0.5 µg/ml, being either equal in activity to ciprofloxacin or two- to four-fold less active, depending upon the species. BMY-40062 was as active as ciprofloxacin againstPseudomonas aeruginosa (MIC90 0.5 µg/ml) and inhibited most other strains ofPseudomonas species at < 1 µg/ml. It was more active than ciprofloxacin or ofloxacin against hemolytic streptococci andStreptococcus pneumoniae, 90 % of strains being inhibited at < 0.5 µg/ml. MICs increased in the presence of 9 mM Mg²⁺ and at pH 5.5. The frequency of spontaneous mutation was low forEnterobacteriaceae, Pseudomonas aeruginosa andStaphylococcus aureus (10^–10), but repeated exposure to BMY-40062 caused selection of resistant isolates. Clinical isolates ofPseudomonas aeruginosa resistant to ciprofloxacin and ofloxacin were resistant to BMY-40062.     

Comparative in vitro activity of the new oral macrolide azithromycin

The in vitro activity of the new oral macrolide azithromycin was compared with that of erythromycin against gram-positive and gram-negative aerobic and anaerobic bacteria. Ninety percent of hemolytic streptococci groups A and B, andStreptococcus pneumoniae were inhibited by 0.5 µg/ml. Activity of azithromycin was similar to that of erythromycin; erythromycin-resistant staphylococci and streptococci were not inhibited. Azithromycin was more active than erythromycin againstHaemophilus influenzae (MIC90 1 µg/ml) andNeisseria gonorrhoeae. It inhibitedCampylobacter spp. andPasteurella multocida, and had an MIC50 of 8 µg/ml forEscherichia coli, Salmonella spp.,Shigella spp. andYersinia enterocolitica compared to an erythromycin value of > 64 µg/ml.     

Comparative antibacterial activity of the new oral cephalosporin BMY-28100

The in vitro activity of BMY-28100 was compared with that of four other oral cephalosporins against gram-positive cocci,Branhamella catarrhalis and Haemophilus influenzae.BMY-28100 showed 5–20 times better activity against staphylococci and streptococci. Methicillin-resistant staphylococci and enterococci were resistant to the drug.Branhamella catarrhalis and Haemophilus influenzae strains were moderately susceptible. Time-kill curve studies showed BMY-28100 to be equally as active as benzylpenicillin, amoxycillin, flucloxacillin and cefaclor. By virtue of its in vitro spectrum, BMY-28100 can be considered a potentially useful agent for treatment of respiratory tract infections.     

Comparative in vitro activity of the new oral cephalosporin cefixime

Cefixime was 8 to 10 times more active than cefaclor and augmentin against isolates of Escherichia coli, Klebsiella pneumoniae and Salmonella typhi, MIC90 values ranging from 0.06 to 0.25 micrograms/ml. However, none of these three drugs was particularly active against isolates of more resistant gram-negative bacilli such as Enterobacter, Serratia, Citrobacter, Acinetobacter, Providencia and Achromobacter spp. The lowest MIC values for gram-negative bacilli were seen with ciprofloxacin, except for isolates of Acinetobacter, where cotrimoxazole was the most active of the five drugs studied. Augmentin and ciprofloxacin exhibited the lowest MICs for isolates of streptococci and corynebacteria. Although cefixime may be among the most active oral beta-lactam drugs, it does not appear to be useful for treatment of infections caused by more resistant gram-negative bacilli.     

In vitro activity of the new ketolide HMR 3004 compared to an azalide and macrolides againstStreptococcus pneumoniae andHaemophilus influenzae

The purpose of this study was to compare the in vitro activity of a new ketolide, HMR 3004 (RU64004), to that of three macrolides and one azalide against 608 Streptococcus pneumoniae and 202 Haemophilus influenzae. Macrolide-resistant pneumococci were susceptible to HMR 3004, even if they were resistant to clindamycin. Against Haemophilus influenzae, HMR 3004 and azithromycin were nearly identical in potency; the macrolides were 8- to 16-fold less active. HMR 3004 may be useful for treating respiratory tract infections if sufficient concentrations can be achieved at the local sites of infection.     

Comparative in vitro activity of the new oral cephalosporin BMY-28100

Using a broth microdilution method, the in vitro activity of BMY-28100 against 365 clinical strains of commonly isolated bacteria was determined. BMY-28100 showed good activity against streptococci, methicillin-susceptible staphylococci,Salmonella spp.,Shigella spp., and beta-lactamase producing Branhamella catorrhalis and Haemophilus influenzae.Against susceptible strains of these organisms, BMY-28100 showed activity comparable to that of penicillin G, ampicillin, co-trimoxazole, erythromycin, cefaclor, doxycycline and amoxicillin/potassium clavulanate. BMY-28100 had moderate activity against Arizona hinshawii and poor activity against Campylobacter jejuni and Yersinia enterocolitica.     

Comparative antibacterial activity of the new cephalosporin cefcanel against anaerobic bacteria

The activity of cefcanel against anaerobic cocci,Clostridium perfringens, Bacteroides fragilis, Bacteroides spp. and fusobacteria was determined by the agar dilution method and compared with the activity of cefaclor, cephalexin, cefadroxil, phenoxymethylpenicillin and ampicillin. Cefcanel showed good activity againstClostridium perfringens, Bacteroides spp. and fusobacteria (MIC90=1–4 mg/l). Against anaerobic cocci its MIC90 value was 16 mg/l, and againstBacteroides fragilis, 32 mg/l. Cefcanel has an antibacterial activity that warrants investigation in clinical trials.