zithromax and quinupristin-dalfopristin

The linkage between internal ribosomal symmetry and transfer RNA (tRNA) positioning confirmed positional catalysis of amino-acid polymerization. Peptide bonds are formed concurrently with tRNA-3' end rotatory motion, in conjunction with the overall messenger RNA (mRNA)/tRNA translocation. Accurate substrate alignment, mandatory for the processivity of protein biosynthesis, is governed by remote interactions. Inherent flexibility of a conserved nucleotide, anchoring the rotatory motion, facilitates chirality discrimination and antibiotics synergism. Potential tRNA interactions explain the universality of the tRNA CCA-end and P-site preference of initial tRNA. The interactions of protein L2 tail with the symmetry-related region periphery explain its conservation and its contributions to nascent chain elongation.

Topics: Amino Acids; Anti-Bacterial Agents; Azithromycin; Catalysis; Crystallography, X-Ray; Models, Molecular; Peptides; Protein Isoforms; Protein Structure, Tertiary; Protein Transport; Ribosomes; RNA, Messenger; RNA, Transfer; Substrate Specificity; Virginiamycin

Macrolides are the primary drugs of choice for a number of clinically significant infections in children. The clinical aspects of newer macrolides such as roxithromycin, clarithromycin, dirithromycin, flurithromycin, miocamycin, rokitamycin, azithromycin and RP 59500 are discussed in different pediatric infections including streptococcal infections (e.g. pharyngitis, otitis, pneumonia, skin infections), staphylococcus soft tissue infections, mycoplasma pneumonia, chlamydial infections as well as legionellosis and campylobacter enteritis. Also, incidences of adverse events in pediatric patients receiving different macrolides are indicated as well as the dosages in children. The advantages of newer macrolides are: lower dosages, b.i.d. or once daily dosage regimens, good intracellular and tissue penetration, better activity against gram-negative microorganisms (some) and a low rate of adverse reactions.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Child; Child, Preschool; Clinical Trials as Topic; Erythromycin; Humans; Infant; Virginiamycin

Antibacterial agents are used in malaria therapy due to their effect on two prokaryote organelles, the mitochondrion and the apicoplast. We demonstrate here that the ribosome-blocking antibiotics telithromycin and quinupristin-dalfopristin, but not linezolid, inhibit the growth of Plasmodium falciparum. Both drugs induce delayed death in the parasite, suggesting that their effect involves the impairment of apicoplast translation processes.

Topics: Animals; Humans; Ketolides; Malaria, Falciparum; Parasitic Sensitivity Tests; Plasmodium falciparum; Protein Biosynthesis; Protein Synthesis Inhibitors; Time Factors; Virginiamycin

Among 203 strains of Staphylococcus aureus, the MICs of CG400549 were 0.06 to 1.0 microg/ml, with MIC(50) and MIC(90) values of 0.25 microg/ml each. All strains were susceptible to linezolid and quinupristin-dalfopristin (MICs, 0.25 to 2.0 microg/ml). The daptomycin MICs were 0.25 to 2.0 microg/ml for methicillin-susceptible and 0.25 to 4.0 microg/ml against methicillin-resistant strains (including vancomycin-intermediate strains). Single-passage selection testing showed low resistance frequencies with CG400549, but multistep analysis showed that CG400549 yielded resistant mutants after 14 to 17 days in all strains tested.

Topics: Acetamides; Anti-Bacterial Agents; Daptomycin; Drug Resistance, Multiple, Bacterial; Enoyl-(Acyl-Carrier-Protein) Reductase (NADH); Enzyme Inhibitors; Linezolid; Methicillin Resistance; Microbial Sensitivity Tests; Molecular Structure; Oxazolidinones; Pyridines; Staphylococcus aureus; Thienopyridines; Thiophenes; Virginiamycin

We evaluated a human monocyte cell line (HL-60) as a model for testing the intracellular activity of anti-Legionella antibiotics; 1.5 x 10(6) HL-60 cells/well were differentiated into adherent cells and infected with 1.5 x 10(7) cfu of Legionella pneumophila. The most active agents against L. pneumophila as judged by broth dilution MICs were (in order of activity) azithromycin, clarithromycin, roxithromycin, quinupristin/dalfopristin, erythromycin and dirithromycin. The most active inhibitors of L. pneumophila intracellular multiplication were (in order of activity) azithromycin, erythromycin, quinupristin/dalfopristin, roxithromycin, dirithromycin and clarithromycin. All the agents were highly active against Legionella micdadei and Legionella bozemanii when compared with L. pneumophila.

Topics: Anti-Bacterial Agents; Azithromycin; Cell Line; Clarithromycin; Erythromycin; HL-60 Cells; Humans; Legionella; Legionella pneumophila; Macrolides; Microbial Sensitivity Tests; Monocytes; Roxithromycin; Virginiamycin

RP 59,500 (Quinupristin-Dalfopristin) is the first semisynthetic injectable streptogramin antimicrobial agent, which is a combination of quinupristin and dalfopristin in a 30:70 ratio. The components of RP 59,500 act synergically to provide bactericidal activity through action at different sites on bacterial ribosomes. In the present study, the antimicrobial activity of RP 59,500 was compared with those of four macrolides (erythromycin, clarithromycin, azithromycin, roxithromycin). Susceptibility testing was carried out by microdilution method on 303 strains of 10 species, especially antibiotic-resistant Gram-positive cocci. RP 59,500 was active against a wide range of Gram-positive cocci including methicillin-resistant Staphylococci and penicillin-resistant Streptococcus pneumoniae. The MICs90 of RP 59,500 against methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis were both 0.25 microgram/ml, although those of four macrolides were higher than 32 micrograms/ml. The MICs90 of RP 59,500 against penicillin-sensitive, -intermediate and -resistant S. pneumoniae were all 0.5 microgram/ml, although those of four macrolides against penicillin-resistant S. pneumoniae were higher than 32 micrograms/ml. RP 59,500 also exhibited equivalent activities to the four macrolides against strains of Streptococcus pyogenes. Streptococcus agalactiae and Moraxella catarrhalis. RP 59,500 exhibited the highest activities against Enterococcus faecalis, Enterococcus faecium and Enterococcus avium strains which are intrinsically resistant to most antimicrobial agents. No cross-resistance was observed between RP 59,500 and the four macrolides, which will merit attention in future clinical trials of the agent. The effect of human serum on the MIC of RP 59,500 was studied with strains of S. aureus, S. epidermidis and E. faecalis. The presence of 20% (V/V) serum had little or no effect on the MIC, although 50% (V/V) serum increased MICs by 4-8 folds. Laboratory-induced resistance to RP 59,500 occurred in a stepwise fashion in broth cultures of S. aureus, S. epidermidis and E. facalis strains and the induction rate was slow and no more than four fold increases were observed. Population analysis was performed on RP 59,500 and the reference macrolides against S. aureus ATCC 25,923 strain. Although low frequencies (less than 0.01%) of resistant sub-population were detected with EM, CAM, AZM and RXM, no RP 59,500-resistant sub-population was detected in this st

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; Enterococcus; Erythromycin; Gram-Positive Cocci; Humans; Methicillin Resistance; Roxithromycin; Staphylococcus aureus; Streptococcus agalactiae; Streptococcus pneumoniae; Streptococcus pyogenes; Virginiamycin

RP 59500 is a 30:70 mixture of RP 57669 and RP 54476. The activity of RP 59500 and its two components against Gram-positive and Gram-negative organisms was compared with that of clarithromycin, roxithromycin, azithromycin and rokitamycin. RP 59500 inhibited 90% of erythromycin-susceptible and resistant Staphylococcus aureus and coagulase-negative staphylococci at less than or equal to 1 mg/L (range 0.06-2 mg/L). Both inducibly and constitutively-resistant strains of S. aureus, as well as strains resistant to rifampicin, gentamicin and ciprofloxacin, were inhibited. Streptococcus pyogenes, including erythromycin-resistant isolates, and group C and G streptococci were inhibited by 0.5 mg/L. Streptococcus pneumoniae and viridans group streptococci were inhibited by 1 mg/L. The MIC90 was 4 mg/L for Haemophilus influenzae and 1 mg/L for Moraxella catarrhalis. RP 59500 did not inhibit Enterobacteriaceae or Pseudomonas aeruginosa. The activity of RP 59500 against streptococci was less than that of the four other macrolides. Clostridium perfringens strains were highly susceptible, as were Bacteroides spp. RP 59500, when combined with ciprofloxacin, cefotaxime or gentamicin, did not have altered activity against susceptible species or alter the activity of the other component of the combination against susceptible species. MBCs in serum were increased two- to four-fold for S. pyogenes, S. pneumoniae and S. aureus, compared with MBCs in broth, but RP 59500 was as active at pH 6 as at pH 7, and there was not an appreciable inoculum effect. RP 59500 has potential use as an agent against inducibly and constitutively erythromycin-resistant isolates of Gram-positive species and selected anaerobic organisms.

Topics: Azithromycin; Bacteria; Cefotaxime; Ciprofloxacin; Clarithromycin; Drug Resistance, Microbial; Drug Therapy, Combination; Erythromycin; Gentamicins; Gram-Negative Bacteria; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Miocamycin; Roxithromycin; Virginiamycin

The in-vitro activities of azithromycin, clarithromycin, spiramycin and RP 59500 were compared with erythromycin against a wide range of oral organisms which have been implicated in oral infections and/or endocarditis (clindamycin was included for oral streptococci). All compounds tested showed good activity against many of these organisms, although some variation was observed with different species. Clarithromycin was the most active of the antibiotics tested against Gram-positive anaerobes, including Actinomyces spp., Propionibacterium spp., Lactobacillus spp. and Bifidobacterium dentium. Azithromycin was slightly less active than erythromycin against these species. In general, RP 59500 had higher MICs than the macrolides, other than spiramycin, against these organisms, but was superior in activity against Peptostreptococcus spp., inhibiting all isolates at 2 mg/L. Azithromycin was, in general, the most active antibiotic tested against the Gram-negative anaerobes: Fusobacterium spp., Bacteroides spp., Wolinella spp., Actinobacillus actinomycetemcomitans, Selenomonas spp. and Mitsuokella multiacida, including those isolates which were insusceptible to erythromycin. Clarithromycin showed similar activity to erythromycin against most Gram-negative species, but was superior against Capnocytophaga ochraceus and Eikenella corrodens. RP 59500 was less active than the macrolides against most Gram-negative anaerobes, but was superior to erythromycin and clarithromycin against Fusobacterium spp. and Leptotrichia buccalis, some strains of which were moderately resistant to erythromycin. The macrolides and clindamycin were about equally active against the oral streptococci, whereas RP 59500 showed lower inhibitory activity. The in-vitro results suggest that azithromycin and clarithromycin may be of value in the treatment of dental sepsis and the prophylaxis of endocarditis. RP 59500 showed useful activity against Gram-positive anaerobes and, because of its bactericidal activity against oral streptococci, may also prove to have a role in these areas.

Topics: Anti-Bacterial Agents; Azithromycin; Bacteria; Bacteria, Anaerobic; Erythromycin; Microbial Sensitivity Tests; Mouth; Streptococcus; Virginiamycin