New directions for macrolide antibiotics: structural modifications and in vitro activity

Kirst, Herbert A.; Sides, Gregory D.

doi:10.1128/aac.33.9.1413

Cited by 152 publications

(64 citation statements)

References 70 publications

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“…3,4 Azithromycin is one such drug with excellent in vitro activity against a wide spectrum of bacteria that includes many aerobic and anaerobic gram positive species and inhibits a number of clinically important intracellular pathogens like S. typhi, Chlamydia, Mycoplasma and Legionella. [2][3][4][17][18][19][20] We found that azithromycin was two to eight times less active than erythromycin against our isolates of staphylococci and streptococci, but more potent against H. influenzae and S. typhi. In addition to in vitro antibacterial activity, the pharmacokinetic properties are important factors in the therapeutic value of a chemotherapeutic agent.…”

Section: Discussionmentioning

confidence: 99%

In VitroActivity of Azithromycin: a Long-Acting Azalide

Qadri

Ueno

Tullo

et al. 1994

Annals of Saudi Medicine

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The in vitro activity of azithromycin, an orally active azalide, was compared with that of erythromycin and oral beta-lactams against 893 clinical isolates of staphylococci, streptococci, enterococci, Haemophilus influenzae and Salmonella typhi. MIC 90 of azithromycin for streptococci was 0.12 mg/L, 0. Azithromycin is an orally active azalide antibiotic with a chemical structure of 9-deoxo-9a-aza-9a-methyl-9a-homoerythromycin A, molecular formula of C 38 H 72 O 12 N 2 , 2H 2 O and molecular weight of 785.01 Kd.1 It contains an aza-methyl substitution at position 9a of the 15-member aglycone ring as compared to 14-member erythromycin.24 Insertion of nitrogen into the lactone ring has been reported to increase its antibacterial activity against gram negative bacteria.1,2 We compared the in vitro activity of this compound with erythromycin and other oral beta-lactam drugs against clinical isolates of staphylococci, streptococci, enterococci, Haemophilus influenzae and Salmonella typhi. Material and MethodsClinical isolates from 893 patients at the King Faisal Specialist Hospital and Research Centre (KFSH&RC) were used for comparative in vitro evaluation of azithromycin. KFSH&RC is a 500-bed tertiary care referral facility in Riyadh, Saudi Arabia. Bacterial isolates were identified by standard routine laboratory procedures.5 Antimicrobial susceptibility testing was performed by the agar dilution method as recommended by the National Committee for Clinical Laboratory Standards.6 Mueller-Hinton agar with or without 5% sheep blood (Difco Laboratories, Detroit, MI, USA) with a pH between 7.2 and 7.4, was used throughout the study except for H. influenzae, where chocolate agar was used. The bacterial suspensions were adjusted to 10 7 CFU/ml and inoculated onto the agarsurface with a multipoint inoculator to contain 10 4 CFU/spot. All incubations were at 35°C for 18 to 24 hours. Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853 and Staphylococcus aureus ATCC 29213 were used as quality control (QC) organisms. The QC results were found to be within the normal expected range during the period of this study. ResultsA total of 893 isolates, consisting of 393 staphylococci, 228 streptococci, 210 H. influenzae and 62 strains of S. typhi were used to evaluate the in vitro activity of azithromycin and the results were compared with erythromycin, ampicillin, augmentin and cephalexin (Table). MIC 90 of azithromycin for members of the genus Streptococcus was 0.12 mg/L, which was comparable to that of erythromycin. Erythromycin-resistant enterococci had an MIC of >32 mg/L for azithromycin. MIC 50 and MIC 90 of azithromycin for methicillin-susceptible S. aureus were four to eight times higher than erythromycin; like erythromycin, azithromycin had virtually no activity against methicillinresistant S. aureus. All the 210 isolates of H. influenzae were inhibited by <0.5 mg/L of azithromycin, its activity being superior to erythromycin and the beta-lactams tested. A single concentration of 8.0 mg/L of this drug inhibited 97% i...

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Section: Discussionmentioning

confidence: 99%

In VitroActivity of Azithromycin: a Long-Acting Azalide

Qadri

Ueno

Tullo

et al. 1994

Annals of Saudi Medicine

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“…The main building block common to all macrolides is a large and highly substituted 14-, 15-or 16-membered macrolactone ring on which one to three sugar moieties such as cladinose and desosamine are usually attached. The mechanism of action of macrolides is the inhibition of RNA-directed protein synthesis, usually achieved by binding to the 50S subunit of bacterial ribosomes [5,6].…”

Section: Introductionmentioning

confidence: 99%

Voltammetric study of the partitioning of macrolide antibiotics at the water/nitrobenzene interface. Relationship to the pharmacokinetic profiling of macrolides

Mandić

2014

ADMET DMPK

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“…Its spectrum includes numerous Gram-positive bacteria, among them staphylococci (Steibigcl, 1990). During the past few years, a resurgence of interest in the macrolides has led to the discovery of several 14-, IS-, and 16-membered derivatives of erythromycin with improved properties (Kirst & Sides, 1989a,A). S-5556 (paranitrobenzyl-oxime-tylosine) is one of the 16-membered compounds descnbed recently (Ruggeri et at., 1989).…”

Section: Introductionmentioning

confidence: 99%

In-vitro and in-vivo evaluation of the antistaphylococcal activity of S-5556, a new 16-membered macrolide

Chuard

Rohner

Dunand

et al. 1992

J Antimicrob Chemother

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During recent years, a resurgence of interest in the macrolides had led to the discovery of new derivatives of erythromycin with improved antibacterial activity and pharmacokinetic properties. In this study the in-vitro and in-vivo antistaphylococcal activity of S-5556, a 16-mciubered macrolide, was evaluated. In vitro, S-5556 was slightly less active than erythromycin against methicillin-susceptible Staphylococcus aureus. In contrast, it had superior activity for methicillin-rcsistant S. aureus (MRSA); several of these strains with inducible resistance to the macrolides-tincosamides-streptogramins group were susceptible to S-5556 whereas erythromycin was inactive. The combination of S-5556 with oxacillin was synergic for most MRSA strains tested. In vivo, a single prophylactic dose of S-5556 prevented 75%-100% of the cases of acute staphylococcal subcutaneous foreign body infection in a guinea pig-model. In a rat-model of chronic implant infection due to a methiciUin-and erythromycin-resistant S. aureus strain, S-5556 significantly decreased the bacteria] concentration around the foreign material, however resistant mutants emerged.

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New directions for macrolide antibiotics: structural modifications and in vitro activity

Cited by 152 publications

References 70 publications

In VitroActivity of Azithromycin: a Long-Acting Azalide

In VitroActivity of Azithromycin: a Long-Acting Azalide

Voltammetric study of the partitioning of macrolide antibiotics at the water/nitrobenzene interface. Relationship to the pharmacokinetic profiling of macrolides

In-vitro and in-vivo evaluation of the antistaphylococcal activity of S-5556, a new 16-membered macrolide

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