Bloodstream infection (BSI) contributes substantially to morbidity and mortality worldwide. In Europe, the annual number of BSI episodes and deaths associated with BSI has been estimated to 1.2 million and 157,000, respectively.

Early diagnosis and early appropriate treatment is crucial. In severe sepsis, the case fatality increases for each hour the antibiotic treatment is delayed. Therefore, empirical antibiotic treatment has to be initiated before the results of blood cultures are available. However, as infections with resistant microbes is an escalating problem worldwide, it is increasingly challenging to maintain appropriate antibiotic regimens for initial empiric therapy.

Resistant pathogenic bacteria are found less frequently in Norway and other Nordic countries, compared to the rest of Europe and other world regions. This probably reflects a relatively restrictive use of antimicrobial agents. In Norway, a regimen containing penicillin and gentamicin (PG), plus metronidazole (PGM) if an anaerobic infection is suspected, has been recommended for more than thirty years in sepsis with unknown focus and etiology. In recent years, however, increasing numbers of infections with methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E), and vancomycin resistant enterococci have been detected.

Selection of inherently resistant microbes due to antibiotic use is also a challenge. Updated knowledge about the distribution of microbes in serious infections and their resistance against antimicrobial agents is needed to ensure appropriate empiric antimicrobial treatment regimens. It is also important to identify subgroups in which tailored regimens are required. Important differences in antibiotic resistance have been found with regard to place of acquisition, and therefore, resistance statistics should specify results for community acquired (CA), health care-associated (HCA), and hospital acquired (HA) infections.

A prospective study was conducted to assess the occurrence and distribution of BSI microbes and their non-susceptibility to some common antibiotic regimens for initial empiric antimicrobial treatment of sepsis of unknown etiology. Particularly, we assessed microbes and antimicrobial resistance by place of acquisition (CA, HCA and HA-BSIs) and with regard to time trends over a 12-year period. We also studied the antibiotic regimens that were used for initial empiric treatment during the same time period and the degree to which they were appropriate.

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