Practice Based Learning: Clindamycin as adjunctive therapy in SSSS

 

 

 

Presented by Kathryn Elkins MD (PGY2)

Clinical question: Is Clindamycin a good adjunctive antibiotic in SSSS?

What antibiotic to start? (Click image to enlarge.)

Where it all began…(Schlievert, et al., 1984)

  • Clindamycin shown to reduce toxin production in TSS causing strains of S. aureus
  • Six typical toxin-producing isolates and one high-toxin producer (MN 8) were evaluated for growth and toxin production in presence of Clindamycin
  • All strains, including the high-toxin producer showed decreased toxin production in presence of clinda, with toxin concentration inversely proportional to clinda concentration.
  • Of note, high-toxin producer growth was NOT inhibited by clinda. Typical strains’ growth was inhibited.

More evidence for Clindamycin (Russell, et al., 2000):

  • Literature search including studies from 1966 to 1999 focusing on role of clindamycin in TSS, specifically evidence to support combination of beta-lactams (drug of choice in TSS) and clindamycin.
  • Many studies showed potential use for clindamycin and suggested possible mechanisms of action including enhanced bacterial opsonization, decreased activation of inflammatory cytokines, no effect of inoculum size, a post-antibiotic effect, and suppression of bacterial toxin production.
  • Despite this, there had been no clinical evidence supporting clindamycin combined with beta-lactams in treatment of TSS!

TSSS vs SSSS:

  • Distribution of genes encoding toxins and virulence factors different between two groups in table
  • Also may account for differences in toxins associated with the different diseases: TSST-1 and enterotoxins are associated with TSS and exfoliative toxins A and B with SSSS
  • No significant difference between TSS and SSS groups for gene encoding exfoliative toxins (eta and etb) associated with SSSS
  • PVL toxin with possible association to TSS; toxin shown in previous studies to cause neutrophil dysfunction
  • Seb is a likely virulence factor associated with TSS, but not much more has been determined per this study
  • FnbB gene associated with adhesion of bacteria to host cell, but unknown association with disease severity
  • Concluded that there are likely associations with certain genes and development of either TSS or SSSS, but more research needs to be done to determine the expression of toxins in strains carrying virulence genes for STSS and SSSS.

Given difference in genes and associated toxins between TSS and SSSS, can I apply same rules to treatment of SSSS?

  • Study from CHOP (Braunstein, et al., 2014) looking at antibiotic resistance patterns and associated risk factors to guide empiric therapy for SSSS.
  • Retrospective chart review from 2005 to 2011
  • 21 patients included in study with staph grown on culture plus susceptibility testing.
  • Compared SSSS causing strains to historical susceptibility S. aureus at CHOP
  • Higher rates of MSSA but clindamycin resistance compared to S. aureus seen in other infections.
  • Do not recommend clindamycin monotherapy
  • Noted that they did not examine toxin production by the isolated organisms and that there may be correlations between antibiotic susceptibility and toxin production that warrant further investigation

Conclusions:

  • Limited studies regarding Clindamycin use in SSSS and most studies are very limited in number of patients and do not take into account regional differences.
  • Studies showing clindamycin reducing toxin production are old and done in vitro. Also focuses on S. aureus that causes Toxic Shock Syndrome and not SSSS.
  • Study from Taiwan suggests there are possible significant genetic differences between S. aureus causing TSS and that causing SSSS – calls into question if same antibiotic therapies recommended (i.e., combination therapy with clindamycin for toxin suppression).
  • Finally, when looking at susceptibilities of S. aureus causing SSSS, significant clindamycin resistance present and so should not use clindamycin as monotherapy and with lack of other studies, there is no evidence that it reduces toxin production for SSSS.
  • May be a good retrospective study here looking at clindamycin use in SSSS? Would have to specifically look at our population, resistance patterns of S. aureus in all staph infections and in those specifically causing SSSS.

References:

Braunstein I, et al. Antibiotic sensitivity and resistance patterns in pediatric staphylococcal scalded skin syndrome. Pediatr Dermatol. 2014 May-Jun;31(3):305-8.

Chi CY, et al. A clinical and microbiological comparison of Staphylococcus aureus toxic shock and scalded skin syndromes in children. Clin Infect Dis. 2006 Jan 15;42(2):181-5.

Russell NE, et al. Clindamycin in the treatment of streptococcal and staphylococcal toxic shock syndromes. Ann Pharmacother. 2000 Jul-Aug;34(7-8): 936-9.

Schlievert PM, Kelly JA. Clindamycin-induced suppression of toxic-shock syndrome–associated exotoxin production. J Infect Dis. 1984 Mar;149(3):471.

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