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Anti-endotoxin immunotherapy in septic shock

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Journal of Antimicrobial Chemotherapy (1987) 19, 551-555

Correspondence

Anti-endotoxin immunotherapy in septic shock Sir,

In his leading article on this subject (Cohen, 1986) Dr J. Cohen made the following statement, reported as a personal communica-tion from M. P. Glauser: "Furthermore, reexamination of the data from the original study by Ziegler et al. (1982), suggests that protection from shock was related to the generation of the highly conserved Re anti-bodies, rather than the Re core associated with E. coli J5". In fact, M. P. Glauser never reported unpublished data from Ziegler's study. The mistake was probably a misunder-standing of part of a paper given at the IXth International Congress of Infectious and Parasitic Diseases, Munich, 1986, in which M. P. Glauser reported data from in-vitro studies performed in rabbits by one of us (J. D. Baumgartner) in collaboration with Dr E. Ziegler. These data revealed that immuniza-tion of rabbits with Escherichia coli J5 produced antibodies of two types: (1) anti-bodies to J5 core determinants distal to KDO, which were mainly type-specific and were quantitatively predominant, and (2) antibodies to the lipid A-KDO region, which were less abundant, but highly cross-reactive (Baumgartner et al., 1987). The latter anti-bodies were measured with Re LPS as antigen, since Re LPS is composed only of lipid A and KDO, in contrast to J5 LPS which possesses several additional core sugars. Thus, although these in-vitro results suggest that antibodies to lipid A-KDO are more likely to afford cross-protection after immunization with E. coli J5 than antibodies to J5 LPS core sugars, this has not been demonstrated clinically.

J. D. BAUMGARTNER M. P. GLAUSER Centre Hospitaller Universitaire Vaudois, 1011 Lausanne. Switzerland References

Baumgartner, J. D., O'Brien, T. X., Kirkland, T. N., Glauser, M. P. & Ziegler, E. (1987). Demonstra-tion of cross-reactive antibodies to smooth gram-negative bacteria in E. coli J5 antiserum.

Journal of Infectious Diseases. In press.

Cohen, J. (1986). Anti-endotoxin immunotherapy in septic shock. Journal of Antimicrobial

Chemo-therapy 18, 436-9.

Determining the MICs of /Mactams for

Haemophilus.

Sir,

With regard to Dr Yourassowsky and colleagues' suggestion that the data regarding

Haemophilus influenzae in our recent

publication (Aldridge, Sanders & Marier, 1986) are artefactual, we have the following comments. We are aware of the pitfalls which exist with the broth microdilution method when studying increased inoculum sizes. Whenever our laboratory performs inoculum effect studies we routinely culture 10 y\ of the 100 /il in each well. The growth or no growth of organisms is then used in those cases of questionable MICs to establish if viable organisms are present. With reference to the

H. influenzae data in question, where an

inoculum effect was evident the growth of viable organisms was demonstrated in all cases. The MBC determinations were not reported because no standardized MBC method has yet been approved in the United States.

We remind Yourassowsky et al. that the inoculum effect with ampicillin has been described with /Mactamase positive and negative strains of H. influenzae at inoculum sizes equal to or greater than 106 cfu/ml

(Thornsberry & Kirven, 1974). Thus with an inoculum size of 106 cfu/ml, even in the

presence of a /Mactamase inhibitor, it is not surprising, as in our study to see a significant inoculum effect since this has been described for /Mactamase negative strains. In addition a number of reports have described a significant inoculum effect when testing cephalosporins against /Mactamase positive and negative strains of H. influenzae (Jones & Preston,

1983; Bell & Washington, 1977).

In our experience doing susceptibility testing of H. influenzae by the broth micro-dilution has not produced excessive problems in MIC endpoint determination nor have we had problems reproducing results. As a matter of fact the use of the broth microdilution method for susceptibility testing of

H. influenzae has been sanctioned by the

National Committee for Clinical Laboratory Standards (1985) in the United States.

Finally, the differences seen between Yourassowsky and colleagues' results and ours cannot be adequately explained at this time. 551

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