Matt Harmon

188 Chapter nine antibiotic resistance of organisms due to prophylaxis. 20 At present, resistance during SDD treatment is low, at least in countries with low resistance rates. 21,22 However, we did not collect data on adverse effects of prophylactic antibiotics, which besides resistance also include drug reactions, drug interactions, etc. Our initial analysis showed a statistically significant association between prophylactic antibiotics and reduction of infections. After accounting for potential clustering in participating TTM centers, the association between prophylactic antibiotics and reduction of infections was lost. In order to have generalizable inferences of the effect of prophylactic antibiotics on outcome, centers must be taken into account, however accounting for a center effect reduces the statistical power. Thereby, it remains unclear from our study whether antibiotics reduce the infection risk unrelated to a center effect. Given that the incidence of nosocomial infection is high in the cardiac arrest population, and that infection contributes to adverse outcome in these patients, investigations of the risk-benefit of prophylaxis in future randomized trials is warranted, including the optimal type of antibiotics as well as the duration of prophylaxis. There are several limitations to this study. Recognizing fever as a sign of infection is hampered during TTM, which may lead to under-diagnosis. Also, frequency of taking cultures was not pre-specified and may have differed between centers. In particular, centers using SDD may have cultured more often than centers not using SD, thereby skewing results. However, this would have probably resulted in more infections in the SDD centers instead of less. Data on microbiological cultures were collected retrospectively and results from this study should be considered within the limitations of this design. As an example, tracheal aspirates were not further specified as protected vs. unprotected. Second, we did not perform a quantitative analysis with broncho-alveolar lavage, and positive cultures of tracheal aspirates could also reflect colonization. However, the effects of prophylaxis were also seen on the incidence of bacteremia. Finally, not all TTM centers participated in this substudy and this may have induced systematic bias. However, patients in the TTM were stratified per center and patients were missing from both large and small centers. We believe this study’s cohort is a fair representation of cardiac arrest patients treated with TTM. Conclusions Gram-negative pathogens are the most common causes of nosocomial infections following cardiac arrest, irrespective of different TTM strategies. It remains unclear whether patients in centers using antibiotic have a reduced incidence of pneumonia and bacteremia that is unrelated to center effects.