The challenge of antimicrobial resistance

7 Examples of pathological threats

- The microbiological battle becomes tougher

The following examples of pathological threats are now part of the daily fight against of infectious diseases:

• Clostridium difficile (C. difficile) causes deadly diarrhea mostly in people who have recently had medical care and antimicrobials.

• Carbapenem-resistant Enterobacteriaceae (CRE) are nightmare bacteria that are resistant to nearly all antimicrobials and spread easily. Almost half of hospital patients in the US who get bloodstream infections from CRE bacteria die from the infection.

• Multidrug-resistant (MDR) Neisseria gonorrhoeae causes gonorrhea and shows resistance to the commonly used antimicrobials.

• Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL) are bacteria one step away from becoming CRE. ESBL is an enzyme that allows bacteria to become resistant to a wide variety of Penicillins and Cephalosporins, including extended spectrum Cephalosporins.

• Multidrug-resistant (MDR) Salmonella is a frequent cause of bacterial intestinal infections and causes about 100,000 illnesses in the US each year; resistant infections are more severe.

• Methicillin-resistant Staphylococcus aureus (MRSA) causes skin and wound infections, pneumonia, and bloodstream infections. Staphylococcus bacteria are one of the most common causes of hospital acquired infections.

• Multidrug-resistant (MDR) Pseudomonas cause hospital acquired pneumonia and bloodstream infections; some strains are resistant to nearly all antimicrobials.

Mechanisms of antimicrobial resistance

– It is a natural phenomenon

Acquired antimicrobial resistance is resistance of a microorganism to an antimicrobial drug that was originally effective for treatment of infections caused by the microorganism. Resistant microorganisms are able to withstand attack by antimicrobial drugs so that standard treatments become ineffective and infections persist, increasing the risk of spreading the resistant microorganism to others. The evolution of resistant microbial strains is a natural phenomenon that occurs when microorganisms replicate themselves erroneously or when resistance genes are exchanged between them. The use and misuse of antimicrobial drugs accelerates the emergence of drug-resistant strains. Poor infection control, inadequate sanitary conditions, and inappropriate food handling also encourages the further spread of antimicrobial resistance.

History of resistance

– There is nothing in the pipeline

The already small and dwindling pipeline of antimicrobial drug candidates makes it unlikely that the rescue will come from newly discovered drugs. Between 1935 and 1968, 14 different classes of antimicrobials were developed. In the 47 years since 1968, only five have been brought out. No new classes have been developed since 1987. One problem is the missing profit potential: profit depends on volume. Many pharmaceutical companies have pulled out of antimicrobial drug development, and instead focus on drugs for chronic conditions, such as diabetes or blood pressure, where the patient is medicated for their whole life. Not surprisingly, this is more profitable than selling drugs for medical ordinations lasting just days or weeks.

Treatment quality

- Consumption and misuse of antimicrobials

Convincing evidence points at the relation between increased antimicrobial consumption and higher levels of antimicrobial resistance [1]. Therefore, it is quite controversial that surveillance data from European Centre for Disease Prevention and Control (ECDC) shows a huge variation in the usage and prescription of antimicrobials among the European countries. Even more striking is it that the usage of Quinolones, Cephalosporins and other broad-spectrum antimicrobials such as Piperacillin/tazobactam is increasing. Despite the change from narrow-spectrum antimicrobials Center for Disease Control (CDC) states that the empirical coverage of microbiologically documented infections is around 50-70%, and that around 50% of all antimicrobial use is inappropriate meaning one of the following:

• Antimicrobials are given when they are not needed
• Antimicrobials are continued when they are no longer necessary
• Antimicrobials are given at the wrong dose
• Broad spectrum agents are used to treat very susceptible bacteria
• The wrong antimicrobial is given to treat an infection

Inappropriate antimicrobial use not only fails to help patients, it may also cause harm. Like every other drug, antimicrobials have side effects and can also interact or interfere with the effects of other medicines. The inappropriate use of antimicrobials unnecessarily promotes antimicrobial resistance at increasing speed if nothing is done.

Consumption of antimicrobials for systemic use (ATC group JO1) at ATC group level 3 in the community, EU/EER countries, 2012, expressed as defined daily dose per 1.000 inhabitants and per day.

1.Sande-Bruinsma van de N, Grundmann H, Verloo D, Tiemersma E, Monen J, Goossens H, Ferech M. European Antimicrobial Resistance Surveillance System Group; European Surveillance of Antimicrobial Consumption Project Group. Antimicrobial drug use and resistance in Europe. Emerg Infect Dis 2008;14:1722-30.

The costs

- We can’t afford antimicrobial resistance in the future

Center for Disease Control (CDC) estimates that in the United States, more than two million people are affected every year by antimicrobial-resistant infections, with at least 23,000 dying as a result. The estimates are based on conservative assumptions and are likely minimum estimates. The estimates have translated into several approximations of the costs of increasing resistance in the United States. The total economic cost of antimicrobial resistance is difficult to calculate, but estimates have ranged as high as $20 billion in excess direct healthcare costs, with additional costs to society for lost productivity as high as $35 billion per year. Examples of the estimates of the costs be center for disease control of individual resistant pathogens are shown below:

References to information on antimicrobial resistance

Below you can find links to more information about the challenge of antimicrobial resistance from the perspectives of the Centre for Disease Control (CDC), the European Centre for Disease Control (ECDC) and the World Health Organization (WHO).

Centre for Disease Control
The World Health Organization