Active and Passive Immunization Protects against Lethal, Extreme Drug Resistant-Acinetobacter baumannii Infection

Extreme-drug-resistant (XDR) Acinetobacter baumannii is a rapidly emerging pathogen causing infections with unacceptably high mortality rates due to inadequate available treatment. New methods to prevent and treat such infections are a critical unmet medical need. To conduct a rational vaccine discovery program, OmpA was identified as the primary target of humoral immune response after intravenous infection by A. baumannii in mice. OmpA was >99% conserved at the amino acid level across clinical isolates harvested between 1951 and 2009 from cerebrospinal fluid, blood, lung, and wound infections, including carbapenem-resistant isolates, and was ≥89% conserved among other sequenced strains, but had minimal homology to the human proteome. Vaccination of diabetic mice with recombinant OmpA (rOmpA) with aluminum hydroxide adjuvant markedly improved survival and reduced tissue bacterial burden in mice infected intravenously. Vaccination induced high titers of anti-OmpA antibodies, the levels of which correlated with survival in mice. Passive transfer with immune sera recapitulated protection. Immune sera did not enhance complement-mediated killing but did enhance opsonophagocytic killing of A. baumannii. These results define active and passive immunization strategies to prevent and treat highly lethal, XDR A. baumannii infections

Antibiotic resistance – why is the problem so difficult to solve?

Antibiotic resistance has been increasing along with antibiotic use. At the same time, the supply of new drugs to replace those rendered inefficient by the development has been dwindling, leading to concerns that we may soon lack efficient means to treat bacterial infections. Though the problem has received considerable interest, there are no indications that the situation is about to change. The present review maintains that this is because the two objectives - preserving the efficiency of existing drugs and increasing the supply of new ones - are partly opposing. Hence, creating an incentive structure compatible with both of them is not easy. Nevertheless, it is suggested that levying a fee on the use of antibiotics, and earmarking the proceeds from this fee for subsidizing development of new antibiotics, would be an important step towards increasing incentives for a better antibiotic stewardship while preserving incentives to develop new substances