NCOH-AMR. Prevention Strategies (PS) Continued efforts are needed in the development and implementation of infection prevention strategies that will be translated into evidence-based protocols and guidelines. Especially for hospital-acquired bacterial infections (e.g. methicillin-resistant S. aureus (MRSA), ESBL/CP-producing bacteria, vancomycin-resistant enterococci), infection prevention measures are important tools in preventing hospital outbreaks of resistant bacteria. Furthermore, more efficient preventive strategies are needed in high-risk populations, such as critically ill patients, transplant recipients and otherwise immunocompromised subjects, to improve patient outcome and to reduce antibiotic use. For controversial approaches, such as using topical antibiotics to prevent infections in the intensive care unit3,4 or after surgery5, the ecological risks for selecting resistance must be balanced against the benefits for patients and society (in terms of costs). As for treatment strategies, large-scale well-designed clinical studies are needed to quantify the effects of prevention strategies.
NCOH-AMR. Frontline Diagnostics (FD) Many infections are treated empirically, i.e., without identification of the causative pathogen. Moreover, in many cases the causative pathogen of infection remains unidentified, leading to unnecessary as well as inappropriate antibiotic use. For instance, it is estimated that about 70% of community-acquired respiratory infections in humans are of viral origin. Most of these infections can be treated safely without antibiotics, especially in ambulatory patients. Yet, a ‘better safe than sorry’ attitude of many physicians in combination with patient pressure leads to frequent antibiotic prescriptions. In hospitals, physicians increasingly treat infected patients with last resort antibiotics in anticipation of an antibiotic-resistant pathogen, as susceptibility results will only be available after at least 24 hours (and usually more). Diagnostics that rapidly (at the point of care) provide reliable results, at low costs, are needed to counteract these practices.
NCOH-AMR. Treatment Strategies (TS) Unnecessary use of broad-spectrum treatment strategies is another aspect of inappropriate antibiotic use. For instance, based on retrospective analyses it has been proposed that patients with community-acquired pneumonia should be treated with a combination of a β-lactam and a macrolide antibiotic, or otherwise with a new fluoroquinolone, instead of β-lactam monotherapy. Both the combination therapy and the new fluoroquinolone augment the antibiotic spectrum, thereby increasing the selective pressure for antibiotic resistance. We recently demonstrated the non-inferiority of the “narrow-spectrum approach”6 and more well-designed clinical studies are needed to change guideline recommendations, currently favouring broad-spectrum approaches. Similarly, current guidelines for empirical treatment of sepsis include the use of broad-spectrum combination therapy or of carbapenemase antibiotics to cover ESBL- producing bacteria, based on poorly evaluated risk factors. The positive predictive values of these risk factors appeared <10% in the Dutch hospitals, implying that guideline adherence will stimulate unnecessary use of these antibiotics7.
NCOH-AMR. New Antibiotics (NA) Up to the 70’s of the 20th century, novel (classes) of antibiotics became available for human and animal health care at regular intervals. However, in the last four decades only 5 new antibiotics acquired market authorization for treatment of infections in humans. With the obvious discrepancy between a rapid emergence of AMR and an (almost) completely halted pipeline of new classes of antibiotics in the final stages of development, our antibiotic arsenal is rapidly decreasing, and physicians are becoming more and more dependent on a decreasing number of effective ‘last resort’ antibiotics. By introducing novel classes of antibiotics, to which 6 Xxxxxx et al, N Engl J Med, 2015, 372(14):1312.
NCOH-AMR. New Therapeutics (NT) A complementary strategy to the development of new antibiotics is the development of alternative therapeutic modalities, that can either eliminate bacteria without selecting for novel resistance traits, or that modulate the immune response of the host during (or before) infection. Such strategies should be based on mechanisms of action not yet used by existing antibiotics or whose delivery mechanisms are not (or at least less) susceptible to evolutionary resistance pressure, or on better understanding of the innate and humoral immune response to bacterial infections caused by species creating current and future treatment problems because of AMR.
NCOH-AMR. Underpinning Research (UR): Drivers of Emergence and Spread The overall objective of this part of the research agenda of the NCOH-AMR is to provide a better insight in the epidemiology and evolution of AMR, specifically the effect of antimicrobial usage on antimicrobial resistance. Use will be made of molecular techniques, bioinformatics, and large clinical studies that enable to understand the dynamics and population structures of antimicrobial resistance.
