Mortality among recipients of the Merck V710 Staphylococcus aureus vaccine after postoperative S. aureus infections: An analysis of possible contributing host factors

Figures & data

Table 1. Relative mortality rates in patients with postoperative S. aureus infections by vaccination group and preoperative IL2 and IL17a levels

			V710 recipients 15/29 (52%) died in selected sample		Placebo recipients 4/22 (18%) died in selected sample
			Mortality Rate n/m (%)	Relative Risk of Death (undetectable IL /detectable IL)	Mortality Rate n/m (%)	Relative Risk of Death (undetectable IL /detectable IL)
IL2 Level	Day of vaccination	undetectable	12/12 (100%)	5.6	1/13 (8%)	0.2
		detectable	3/17 (18%)		3/9 (33%)
	Day of admission	undetectable	11/11 (100%)	5.6	1/10 (10%)	0.4
		detectable	3/17 (18%)		3/12 (25%)
IL17a Level	Day of vaccination	undetectable	9/10 (90%)	2.8	0/10 (0%)	0
		detectable	6/19 (32%)		4/12 (33%)
	Day of admission	undetectable	10/10 (100%)	4.5	0/10 (0%)	0
		detectable	4/18 (22%)		4/12 (33%)

IL, interleukin; n/m (%), number who died/number in group with the specified interleukin level (mortality rate).

Samples were selected so as to include all S. aureus-infected patients who had died during the study in both the V710 and placebo groups. Approximately the same numbers of S. aureus-infected survivors were obtained by unmatched convenience sampling. Sample selection was constrained by the total of 4 postoperative deaths in S. aureus-infected placebo recipients. Because specimens were not available for all patients at each time point, the denominators vary across cells. As a consequence of how patients were selected for the IL analyses, the pretest mortality rates were 15/29 (52%) and 4/22 (18%) for the respective V710 and placebo groups. The proximate cause of death was not routinely determined.

Figure 1. Log-plot of IL2 and IL17a levels over time in V710 and placebo recipients with postoperative S. aureus infections by survival versus death. Top Panels: IL2 levels. Bottom Panels: IL17a levels. Interleukin (IL) levels were measured with the Milliplex MAP human cytokine assay (EMD Millipore Corp, Merck KGaA, Darmstadt, Germany) having an approximate lower limit of quantification of 0.2–0.6 pg/mL and lower limit of detection (LOD) of ∼0.1 pg/mL. Rank values were compared between patients who survived or died in each group using Mann-Whitney tests adjusted for multiplicity with a Bonferroni correction of 40 (10 cytokines x 4 time points). Accordingly, α = 0.00125 was set as the threshold for statistical significance. The unadjusted p-values are shown at the bottom of each column and designated with an asterisk as significant when ≤0.00125. As summarized in Table 1, IL-values were arbitrarily dichotomized as detectable or undetectable. V710 recipients having preoperative IL-levels below the level of assay detection (both before and after vaccination) were more likely to succumb following postoperative S. aureus infections than similar patients with detectable levels. A comparable relationship between IL levels and death after postoperative S. aureus infections was not apparent in the placebo group, where in contrast to the V710 recipients, the mortality rate was numerically lower in placebo recipients with undetectable IL levels than in similar patients with detectable levels.