How to combat growing threat of antimicrobial resistance
- Copyright © 2015 by the American Academy of Pediatrics
Infections are occurring in the United States that are resistant to all antimicrobial options.
Numerous medical groups have identified increasing antibiotic resistance among both gram-positive and gram-negative bacteria acquired in community or health care settings as a serious threat to public health. The Centers for Disease Control and Prevention (CDC) estimates that more than 2 million people each year in the United States acquire antimicrobial-resistant infections, and more than 23,000 die as a result of the infection.
Antimicrobial resistance applies not only to bacteria but also to fungal infections such as Candida, viruses such as HIV and influenza, parasites such as plasmodia that cause malaria, and Mycobacterium tuberculosis.
Which of the following actions help combat the spread of resistant organisms?
Adherence to the childhood immunization schedule
Limiting use of antibiotics in animal feed
Ensuring appropriate use of antimicrobial agents (antibiotic stewardship)
Promoting the development of new antimicrobial agents
Answer: All four options are important in limiting antimicrobial resistance.
More hospitalized patients in the United States die of methicillin-resistant Staphylococcus aureus infections than from tuberculosis and HIV combined. The following organisms cause the majority of hospital-acquired infections: carbapenem-resistant Klebsiella pneumoniae and other Enterobacteriaceae, including Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species; methicillin-resistant S. aureus; and vancomycin-resistant Enterococcus faecium.
The CDC has identified carbapenem-resistant Enterobacteriaceae, drug-resistant Neisseria gonorrhea and Clostridium difficile as the most urgent threats.
At least 14,000 people die each year in the United States from C. difficile infections, many of which could have been avoided by antibiotic stewardship. Infections identified as serious threats (second level of concern) include fluconazole-resistant Candida, extended spectrum beta-lactamase producing Enterobacteriaceae, multidrug resistant P. aeruginosa, drug-resistant Streptococcus pneumoniae, methicillin-resistant S. aureus and drug-resistant tuberculosis.
Immunization protects against infection from both sensitive and resistant organisms. For example, introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in 2000 resulted in a dramatic decline in pneumococcal disease, including disease caused by antimicrobial nonsusceptible pneumococci in the United States. Over the next few years, disease caused by pneumococcal serotypes with antimicrobial resistance and not included in PCV7 increased. In particular, serotype 19A emerged as a common cause of invasive pneumococcal disease with high rates of antibiotic resistance. Serotype 19F was included in PCV7, but opsonophagocytic antibodies against 19F are not active against 19A. Widespread use of PCV13 since 2010 appears to be reducing rates of disease due to serotype 19A, which is included in the vaccine.
Sub-therapeutic concentrations of antibiotics are used in animal feed to increase the growth of livestock and control animal disease. Many medical and public health groups strongly endorse restrictions on the use of antimicrobial agents for growth promotion among livestock.
Antimicrobial stewardship is designed to optimize the outcome of an infectious disease while minimizing the emergence of resistant bacteria or complications of antimicrobial therapy, such as C difficile infection. Antibiotic stewardship helps ensure a patient receives the correct antimicrobial agent for the proper period of time.
One study evaluated children younger than 18 years of age who were seen in office-based physician practices throughout the United States between 2000 and 2011 because of an acute respiratory tract infection (otitis media, sinusitis, bronchitis, upper respiratory tract infection and pharyngitis) (Kronman MP, et al. Pediatrics. 2014;134:e956-e965OpenUrl). Surveys administered by the National Center for Health Statistics were used to generate national estimates of disease and antibiotic prescribing patterns in this setting. Antimicrobial agents were prescribed during an estimated 56% of the visits. Estimates suggest that about 27% of children in the post-pneumococcal conjugate vaccine era who present with otitis media, sinusitis, bronchitis, upper respiratory infection or pharyngitis will have a bacterial infection that may benefit from antibiotic therapy. Thus, in this analysis, millions of doses of unnecessary antibiotic therapy were administered.
Antibiotics are among the most commonly prescribed drugs. The CDC estimates that up to 50% of all prescribed antibiotics are not needed.
Other strategies suggested by the CDC to control spread of antimicrobial-resistant microbes include development and use of rapid diagnostic tests for identification and characterization of resistant bacteria. In addition, improved surveillance efforts are needed to identify the emergence of resistance patterns.
Restricting antimicrobial use through antimicrobial stewardship programs and limiting the use of medically important antibiotics (useful for treatment of human infections) in feed for livestock are financial disincentives for pharmaceutical companies to develop new classes of agents. Appropriate incentives by the federal government will become increasingly important to maintain drug development. Since it may be years before novel antimicrobials are available to treat certain resistant infections, it is important to improve use of currently available antimicrobial agents.
For more information, see Antibiotic Resistance Threats in the United States, 2013 from the Centers for Disease Control and Prevention, www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf.
View the AAP clinical report, Principles of Judicious Antibiotic Prescribing for Upper Respiratory Tract Infections in Pediatrics at http://pediatrics.aappublications.org/content/132/6/1146.
Dr. Meissner is professor of pediatrics at Floating Hospital for Children, Tufts Medical Center. He also is an ex officio member of the AAP Committee on Infectious Diseases and associate editor of the AAP Visual Red Book.