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Newsletter Vol. 29 No. 2




The Need for Improved Diagnostics: Harder Better Faster Stronger

Jennie Choe, M.S.
Assistant Editor
Alliance for the Prudent Use of Antibiotics

 




Antibiotic resistance is considered by health authorities such as WHO and CDC to be one of the greatest public health threats facing the world today [1]. Staggering rates of mortality, morbidity, and economic cost give weight to this claim. 440,000 cases of multi drug-resistant tuberculosis emerge annually and result in more than 150,000 deaths [2]. Extensively drug-resistant tuberculosis has been reported in 69 countries to date, and most malaria-endemic countries are showing resistance to earlier generation antimalarial drugs. As recently as 2007, MRSA was responsible for more annual deaths than AIDS [3]. An APUA-sponsored study published in Clinical Infectious Diseases also found that in 2000, antibiotic-resistant infections were responsible for anywhere from $18,588 to $29,096 in medical costs per patient, and 6.4 to 12.7 extra days in the hospital. In a single hospital that year the costs of treatment, extended hospital stays, and lost wages added up to $15 million – an estimated $35 billion nationwide [4].

As antibiotic resistance wreaks havoc among individuals, communities, and health facilities, the need has never been greater for effective clinical diagnostic tests. The most valuable diagnostic tests are those that can 1) rapidly identify a pathogen, 2) determine its antibiotic resistance profile, and 3) be used to choose and immediately initiate the best therapy. Ideally, they should also be sensitive and specific, fast, cheap, user-friendly, and ready for use on native samples at a patient’s bedside. These are high standards worth striving for. Early diagnosis and immediate initiation of an appropriate antibiotic treatment can greatly improve the outcomes of many different types of infections. Conversely, during some systemic responses to infection (such as sepsis), every hour of delay in the administration of the right treatment is associated with a 7% rise in mortality [5]. In the case of pathogens that are similar in morphology to harmless bacteria (such as coagulase-positive S. aureus), a mistaken or delayed diagnosis can cause patients to be treated unnecessarily with broad-spectrum antibiotics or to be given inadequate doses of antibiotics – both powerful drivers of resistance.

Unfortunately, many of the “gold standard” diagnostic tests that have been used until now are limited by difficult and time-consuming sample preparation, bulky instruments, slow data readout, and low sensitivity and specificity of detection. However, the field of diagnostic technology is growing rapidly and in exciting new directions. Some cutting-edge diagnostic methods sound futuristic and almost fanciful. For example, an infection can be classified as viral or bacterial, and subsequently attributed to a certain pathogen, by measuring the degree of chemiluminescence exhibited by white blood cells in a specially treated sample of whole blood [6]. Signature sequences in bacterial DNA that give away information about its identity and its resistance or susceptibility to various drugs can be pinpointed using fluorescently tagged peptide nucleic acid (PNA) constructs [7]. Drug resistant bacteria can even be localized within the body through a simple, noninvasive PET scan by commandeering the proteins that the bacteria normally bind to and tagging them with a radioactive isotope [8].

Other methods are really extensions of older technology that was conceived decades ago, but is now being overhauled for new applications. Mass spectrometry has been used for 35 years to identify pathogens based on their protein compositions, but its high-throughput sensitivity has only recently been used to distinguish between bacteria of the same family, genus, and even species but that are susceptible to different antibiotics [9]. These technologies and others like them give us hope that we can look down the development pipeline not only for new diagnostic tools, but perhaps even for companion novel antibiotic drugs.

One of APUA’s most valuable assets since its inception in 1981 has been its ability to bring together diverse stakeholders in discussion and collaboration. In this issue we probed the front lines of the biotechnology industry to get a sampling of insider perspectives on the opaque world of diagnostic device development. Among our contributors for this Newsletter we have expert epidemiologist Dr. Iruka Okeke’s thoughts on the desperate need for a homogenized diagnostic system in Africa, as well as an opinion article from bioMérieux Inc., a world leader in in vitro diagnostics for the past 45 years. We also interviewed research and development experts committed to diagnostic innovation, who are making remarkable advances in the field and that healthcare practitioners everywhere will no doubt keep on their radar.

Diagnosis is the first step. The most innovative and effective treatments, therapies, and miracle drugs can only be put in motion as quickly as the problem can be accurately diagnosed. In the world of infectious disease, delays cause sharp increases in morbidity and mortality. Every wrong prescription makes bacteria more able to evolve into agents that antibiotics may one day be powerless against. APUA and organizations like it will continue working to make sure that day never comes, by promoting infection control, responsible antibiotic stewardship, and incentives for diagnostic innovation. The exploration of new technology and the evolution of diagnosis from slow and misdirecting to immediate and accurate can literally be the pivot point between life and death.
 




References
1. (2011, April 6). World Health Day 2011: Urgent action necessary to safeguard drug treatments. World Health Organization. Retrieved September 1, 2011, from http://www.who.int/mediacentre/news/releases/2011/whd_20110406/en/index.html
2. (2011, February). Antimicrobial Resistance. World Health Organization. Retrieved September 1, 2011, from http://www.who.int/mediacentre/factsheets/fs194/en/
3. (2011, July 5). How Much is a Drug-Resistance Death worth? Less than $600. Wired. Retrieved August 22, 2011, from http://www.wired.com/wiredscience/2011/07/resistance-death-worth/#more-66478
4. Roberts RR, Hota B, Ahmad I, et al. (2009) Hospital and societal costs of antimicrobial-resistant infections in a Chicago teaching hospital: implications for antibiotic stewardship. Clinical Infectious Diseases 49:1175-1184.
5. Dellinger RP, Levy MM, Carlet JM, et al. (2008) Surviving Sepsis Campaign: international guidelines for management of severe sepsis and shock. Critical Care Medicine 36(1):296-327.
6. Prilutsky D, Rogachev B, Marks RS, et al. (2011) Classification of infectious diseases based on chemiluminescent signatures of phagocytes in whole blood. Artificial Intelligence in Medicine 52:153-163.
7. Smolina I, Miller NS, Frank-Kamenetskii MD. (2010) PNA-based microbial pathogen identification and resistance marker detection. Artificial DNA: PNA & XNA 1(2):76-82.
8. Panizzi P, Nahrendorf M, Figueiredo JL, et al. (2011) In vivo detection of Staphylococcus aureus endocarditis by targeting pathogen-specific prothrombin activation. Nature Medicine 17(9):1142-1146.
9. Dubska L, Pilatova K, Dolejska M, et al. (2011) Surface-enhanced laser desorption ionization/time-of-flight (SELDI-TOF) mass spectrometry (MS) as a phenotypic method for rapid identification of antibiotic resistance. Anaerobe. Advance online publication http://www.ncbi.nlm.nih.gov/pubmed/21624485.
 




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