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Chapter 20 : Streptogramins

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Abstract:

The streptogramins form a complex group of unique antibacterial agents. The streptogramins are composed of a mixture of two types of molecules: group A streptogramins and group B streptogramins. Each molecular complex contains both structures, but several compounds of each of the two groups may belong to the complex. The combinations of streptogramins plus aminoglycosides, rifampin, or β-lactams are synergistic. Both streptogramins A and B penetrate the bacterial cell by passive diffusion. Group A streptogramins act on the early stage of the protein synthesis, especially on the elongation phase of translation. Group B streptogramins exert inhibitory activity at the end of the process during extension of the peptide chain, causing premature detachment of the incomplete chain. A new mechanism of resistance was described in 1984: isolated resistance to factor A (pristinamycin IIA) and lincosamides (LSA phenotype) conferring low-level resistance to streptogramins. In the Protek study conducted from 2000 to 2001, it was shown that less than 0.02% of Streptococcus pneumoniae strains are resistant to dalfopristin-quinupristin. Each isolate had a 5-aminoacid tandem duplication in the L22 ribosomal protein gene (rplV), preventing synergistic ribosomal binding of the streptogramin combination. Staphylococcus aureus possesses a hydrolase on the same plasmid that opens the macrolactone ring of pristinamycin IA and causes it to lose its antibacterial activity despite good ribosomal binding. The majority of these S. aureus strains have reduced susceptibility to lincosamides. This chapter also talks about dalfopristin-quinupristin (RP-59500), RPR 106972, and XRP 2868.

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Figures

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Figure 1

Streptogramin A

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Figure 2

Streptogramin B derivatives

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Figure 3

Etamycin (viridogriseine)

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Figure 4

Pristinamycin I

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Figure 5

Mechanism of action of streptogramins

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Figure 6

Pristinamycin IA and IIA derivatives

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Figure 7

Comparative activity of the 5δ-thiomethyl pristinamycin IA derivatives against S. aureus (adapted from Barrière et al.)

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Figure 8

Pristinamycin IA derivatives

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Figure 9

Dalfopristin-quinupristin

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Figure 10

Oral streptogramin

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Figure 11

XRP 2868

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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References

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Tables

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Table 1

Streptogramins of natural origin

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Table 2

Group A streptogramins

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Table 3

Group B streptogramins

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Table 4

Group B streptogramin derivatives

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Table 5

Solubility of streptogramins (μg/ml)

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Table 6

Comparative activities of natural streptogramins

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Table 7

Antibacterial activity of pristinamycin

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Table 8

Activities of streptogramins against anaerobes

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Table 9

Activity of pristinamycin against intracellular and atypical bacteria

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Table 10

Antibacterial activity of pristinamycin

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Table 11

Prevalence of dalfopristin-quinupristin resistance in Europe

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Table 12

Prevalence of dalfopristin-quinupristin resistance in Taiwan

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Table 13

Staphylococcal resistance phenotypes a

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Table 14

Genes involved in streptogramin resistance

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Table 15

Pharmacokinetics of pristinamycin components after administration of 2 g orally

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Table 16

Pharmacokinetics of pristinamycin and virginiamycin a

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Table 17

Pharmacokinetics of pristinamycins I and II after repeated doses (2 g/day) a

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Table 18

In vitro activity of dalfopristin-quinupristin (I)

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Table 19

In vitro activity of dalfopristin-quinupristin (II)

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Table 20

In vitro activities of dalfopristin-quinupristin and the two components

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Table 21

Endocarditis in rabbits

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Table 22

Pharmacokinetics of dalfopristin-quinupristin after repeated doses

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Table 23

Pharmacokinetics of dalfopristin-quinupristin (RP-59500)

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Table 24

Intravenous pharmacokinetics of dalfopristin and quinupristin a

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Table 25

Pharmacokinetics of dalfopristin-quinupristin in suction blister fluid

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Table 26

Levels of dalfopristin and quinupristin in cerebrospinal fluid

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Table 27

In vitro activity of RPR 106972 and its components

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
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Table 28

Pharmacokinetics of RP-106972 after food

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
Generic image for table
Table 29

Pharmacokinetics of RP-106972

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
Generic image for table
Table 30

In vitro activity of XRP 2868

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20
Generic image for table
Table 31

Activity of XRP 2868 against well-defined S. pneumoniae (genotypes)

Citation: Bryskier A. 2005. Streptogramins, p 570-591. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch20

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