Preventive vaccines for high-risk populations are urgently needed
All business and technical aspects of how humanity is getting into a post-antibiotic era are well summarized in the review “Alternatives to antibiotics-a pipeline portfolio review” by Czaplewski et al. (2016), Lancet Infect Dis. 16(2):239-51, reporting results from The Review on Antimicrobial Resistance, sponsored by the Wellcome Trust and the UK Department of Health (https://amr-review.org).
The final message is that if we do not act at the short term, in 2050, antibiotic-resistant infections will kill 10 million people worldwide, more than the population killed by cancer, and 5-fold the population killed by Covid-19 in 2020.
Today, the population at risk of developing antibiotic-resistant infections worldwide is 100 million. The associated economic losses today are above 40.000 million USD per year, while the expected global losses in 2050 have been forecasted in 100.000 billion USD.
The World Health Organization has published recently a list of the most worrisome bacteria, mainly because their capacity of resistance to all or almost all available antibiotics (https://www.who.int/news/item/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed).
If there is enough investment, prevention will come faster than therapeutics. Prevention will be required in the coming future. All therapeutic alternatives to antibiotics are in very early stages of development. There are concerns about the safety of using bacteriophages and lysins coming from bacteriophages. Also, about their universality and manufacturing. Monoclonal antibodies usually cannot neutralize the infections by targeting only one epitope of the bacterial surface, and having multivalent antibodies for therapy is technically and economically difficult.
It is under this scenario of forecasted dramatic incidence of infections caused by antibiotic-resistant bacteria when there is an urgent need for preventive vaccines. Immunizing the population with high risk, globally, and later extending immunization to other groups in regions specially targeted by the high incidence of infections will transform a dramatic situation into a bearable situation, in which alternative treatments, still in a very early stage of development, will be also required.
There is not vaccine available nor in the clinical phase of development against the most urgent threats from the list of the WHO (Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae like Klebsiella pneumoniae).
Need of raising immunity against antibiotic-resistant threats in people suffering chronical lung disease in the community
Chronic Obstructive Pulmonary Disease (COPD) patients with advanced airflow obstruction are treated with cycles of oral antibiotics.
The subgroup with recurrent severe acute exacerbations must be treated with mechanical ventilation and intravenous antibiotics, rising the risk of development of pneumonia caused by multi-drug resistant P. aeruginosa, K. pneumoniae, and/or A. baumannii with 50% mortality rate associated.
There are 36 million people affected by COPD only in USA+EU (increment of 120.000/year). The prevalence of Pseudomonas aeruginosa or Klebsiella pneumoniae as causative agents of infections in this population is currently 8-15% (and rising).
Need of expanding protection to other risk groups in the community
Today, 13.000.000 people are admitted annually to ICUs only in USA and EU (annual growth circa 15%). The average incidence of ICU-acquired pneumonia in the USA and EU is 5%. Therefore, 650.000 people are affected annually by bacterial pneumonia in the ICUs. Due to the extremely high level of antibiotic-resistance of A. baumannii, the average mortality rate is 43%. Including infections caused by P. aeruginosa and K. pneumoniae, whose incidence as causative agents of ICU-acquired pneumonia in the USA are 22% and 7%, respectively, the number of patients affected today only in USA+EU is estimated to be 227.500 per year.
Globally, the problem increases in magnitude as sanitary conditions are worse outside the first world and the incidence of resistance to antibiotics increases. Conservative estimates of the global incidence consider at least 3-fold the people affected in the USA + EU. The incidence of A. baumannii in ICU-acquired pneumonia worldwide is 15%. The incidences of P. aeruginosa and K. pneumoniae are 27% and 10%, respectively. Together, 1.000.000 people/year are affected by pneumonia caused by either A. baumannii, P. aeruginosa, or K. pneumoniae.
The populations in need of preventive immunity globally comprise chronic lung disease patients, cancer patients, patients subjected to dialysis, patients with chronic liver damage, patients with diabetes, patients in the waiting list for solid-organ transplantation, women with recurrent urinary-tract infections, and neonates, especially in low-and-middle income countries.