Multiresistant nosocomial pathogens often cause life-threatening infections that are sometimes untreatable with currently available antibiotics and are therefore one of the most serious problems in modern medicine. A recent report from the Centers for Disease Control and Prevention (CDC) estimates that in the US about two million people acquire infections with resistant bacteria, and that probably about 23,000 patients die each year as a direct consequence of these infections [
1]. Gram-positive bacteria account for a large proportion, and staphylococci and enterococci are the most important bacterial species causing these mostly hospital-acquired infections that often lead to extended hospital stay and excess mortality. Multiresistant
Staphylococcus aureus cause pneumonia, skin, wound, bloodstream and surgical site infections. About 80,000
S. aureus infections have been reported in the US per year with about 12,000 deaths caused by bacteria resistant to methicillin (MRSA) [
1]. High rates are also seen for enterococci, mainly
Enterococcus faecium resistant to vancomycin (VRE) causing bloodstream infections, urinary tract infections, and foreign-body infections (e.g., catheters, stents, CNS shunts, artificial heart valves, etc.) mostly in immunocompromised patients [
2‐
4]. For the US, it is estimated that about 66,000 enterococcal infections occur each year, and about 20,000 of these are due to multiple-drug resistant (i.e., VRE) with about 1,300 deaths per year [
1]. Multiresistance in Gram-negative bacteria is mostly due to extended-spectrum betalactamases (ESBL) or carbapenemases. ESBL-producing
Enterobacteriaceae are increasingly isolated in patients and even otherwise healthy individuals [
5]. These bacteria can cause bloodstream infections and are responsible for approximately 26,000 cases and 1,700 deaths per year [
1]. Especially worrisome is a novel threat associated with resistance determinants against carbapenems, currently the antibiotics with the broadest spectrum. In the US, more than 9,000 healthcare-associated infections are caused by carbapenem-resistant
Enterobacteriaceae (
K. pneumoniae and E. coli) and 600 deaths result from these infections each year [
1]. Similar trends and incidences have been reported in Europe (
http://www.ecdc.europa.eu/en/activities/surveillance/EARS-Net/Pages/index.aspx).
Immunotherapy, either through active immunization, or by passive immunotherapy, is among the most promising alternative approaches to fight these strains [
4,
6]. While the development of novel vaccines against multiresistant nosocomial pathogens is pursued by many of the leading pharmaceutical companies, no preparation has yet been introduced into the market [
7]. Passive immunotherapy, either through monoclonal antibodies, or through hyperimmunoglobulins, may be an attractive addition to the currently available treatment options. However, no good data exist to support the usage of these preparations to prevent and/or treat infections in hospitalized patients.
Intravenous application of immunoglobulins from healthy volunteers has been used for a number of indications, e.g., immunoglobulin substitution (i.v.) in patients with agammaglobulinemia, and as a supportive therapy for bacterial infections, Kawasaki disease, or Guillain-Barré syndrome. Most currently available antibody preparations contain only IgG and several studies could not demonstrate a benefit of these antibodies in the prevention and treatment of bacterial infections. However, in the initial immune response against bacterial pathogens, IgM plays an important role and the production of a compound containing not only IgG but also IgA and IgM may therefore offer the advantage of an “innate” immune protection against bacteria [
8]. Here, we investigate and compare the efficacy of protection of different antibody preparations with and without IgM and demonstrate that IgM provides a better protection in vivo and in vitro against some nosocomial pathogens.