BAUMGARTNER, J. D.

GLAUSER, M. P.

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Journal of Antimicrobial Chemotherapy (1987) 19, 551-555CorrespondenceAnti-endotoxin immunotherapy in septic shockSir,In his leading article on this subject (Cohen,1986) Dr J. Cohen made the followingstatement, reported as a personal communica-tion from M. P. Glauser: "Furthermore,reexamination of the data from the originalstudy by Ziegler et al. (1982), suggests thatprotection from shock was related to thegeneration of the highly conserved Re anti-bodies, rather than the Re core associatedwith E. coli J5". In fact, M. P. Glauser neverreported unpublished data from Ziegler'sstudy. The mistake was probably a misunder-standing of part of a paper given at the IXthInternational Congress of Infectious andParasitic Diseases, Munich, 1986, in whichM. P. Glauser reported data from in-vitrostudies performed in rabbits by one of us(J. D. Baumgartner) in collaboration with DrE. Ziegler. These data revealed that immuniza-tion of rabbits with Escherichia coli J5produced antibodies of two types: (1) anti-bodies to J5 core determinants distal to KDO,which were mainly type-specific and werequantitatively predominant, and (2) antibodiesto the lipid A-KDO region, which were lessabundant, 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 andKDO, in contrast to J5 LPS which possessesseveral additional core sugars. Thus, althoughthese in-vitro results suggest that antibodies tolipid A-KDO are more likely to afford cross-protection after immunization with E. coli J5than antibodies to J5 LPS core sugars, this hasnot been demonstrated clinically.J. D. BAUMGARTNERM. P. GLAUSERCentre HospitallerUniversitaire Vaudois,1011 Lausanne.SwitzerlandReferencesBaumgartner, J. D., O'Brien, T. X., Kirkland, T. N.,Glauser, M. P. & Ziegler, E. (1987). Demonstra-tion of cross-reactive antibodies to smoothgram-negative bacteria in E. coli J5 antiserum.Journal of Infectious Diseases. In press.Cohen, J. (1986). Anti-endotoxin immunotherapy inseptic shock. Journal of Antimicrobial Chemo-therapy 18, 436-9.Determining the MICs of /Mactams forHaemophilus.Sir,With regard to Dr Yourassowsky andcolleagues' suggestion that the data regardingHaemophilus influenzae in our recentpublication (Aldridge, Sanders & Marier,1986) are artefactual, we have the followingcomments. We are aware of the pitfalls whichexist with the broth microdilution methodwhen studying increased inoculum sizes.Whenever our laboratory performs inoculumeffect studies we routinely culture 10 y\ of the100 /il in each well. The growth or no growthof organisms is then used in those cases ofquestionable MICs to establish if viableorganisms are present. With reference to theH. influenzae data in question, where aninoculum effect was evident the growth ofviable organisms was demonstrated in allcases. The MBC determinations were notreported because no standardized MBCmethod has yet been approved in the UnitedStates.We remind Yourassowsky et al. that theinoculum effect with ampicillin has beendescribed with /Mactamase positive andnegative strains of H. influenzae at inoculumsizes equal to or greater than 106 cfu/ml(Thornsberry & Kirven, 1974). Thus with aninoculum size of 106 cfu/ml, even in thepresence of a /Mactamase inhibitor, it is notsurprising, as in our study to see a significantinoculum effect since this has been describedfor /Mactamase negative strains. In addition anumber of reports have described a significantinoculum effect when testing cephalosporinsagainst /Mactamase positive and negativestrains of H. influenzae (Jones & Preston,1983; Bell & Washington, 1977).In our experience doing susceptibilitytesting of H. influenzae by the broth micro-dilution has not produced excessive problemsin MIC endpoint determination nor have wehad problems reproducing results. As a matterof fact the use of the broth microdilutionmethod for susceptibility testing ofH. influenzae has been sanctioned by theNational Committee for Clinical LaboratoryStandards (1985) in the United States.Finally, the differences seen betweenYourassowsky and colleagues' results and ourscannot be adequately explained at this time.551

Anti-endotoxin immunotherapy in septic shock

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