Historically, infectious diseases have been a primary cause of mortality. With the advent of safe and effective antibiotics in the middle of the 20th century, deaths from bacterial infectious diseases became relatively rare and were no longer considered a pressing medical problem.
A generation ago, many doctors believed that antibiotics had allowed humanity to declare victory in the war against bacterial diseases. Even as recently as 1986, a leading physician and medical educator could declare that "I cannot conceive the need for more infectious disease experts."1
This golden age of antibiotics has ended and is unlikely to return. In the golden age, nearly all bacteria were susceptible to most antibiotics, and physicians could be confident in the efficacy of standard antibiotic therapy protocols. Although resistance to first-generation drugs such as penicillin emerged, these drugs could be replaced by the new discoveries that were regularly emerging from the pharmaceutical industry.
Now, all the low-hanging fruit in antibiotic discovery has been picked clean. New antibiotics are rare and in most instances, offer little to nothing over older antibiotics. Many are so similar to existing agents that resistance emerges within a few years of introduction.
Despite these trends, the management of infectious diseases is little changed. Most antibiotic therapy is empiric (i.e., physicians select antibacterials with little-to-no data to guide their choice). Lacking specific data on resistance and susceptibility, the standard course is to place patients on broad-spectrum agents that have wide but limited efficacy. One of the reasons for this course is that it can take 2-3 days for the receipt of laboratory results that allow optimization of therapy.
Consequently, "inappropriate" (unnecessarily broad spectrum) therapy can continue for long time periods, increasing antibacterial resistance selection pressure.
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Similarly, the rise in methicillin-resistant S. aureus infection has resulted in the opposite problem (i.e. patients often are not adequately covered for this pathogen). Patients with deadly Staphylococcus aureus bloodstream infections, which have mortality rates of greater than 30 percent, receive appropriate antibiotics in only half of all cases.2 The current state of empirical antibacterial treatment for S. aureus has deteriorated to the point that it has been compared to a coin toss.3
The impact of antibiotic resistance on mortality and associated treatment costs is significant. Hospital-acquired bacterial infections now exceed 1.7 million per year in the US, resulting in more than 100,000 deaths.4
Antibiotic resistance is considered a contributing factor in 75 percent or more of these deaths.5 Considering that these data do not include community-acquired infections (principally pneumonia), it is likely that the number of Americans killed by antibiotic resistant bacteria each year exceeds 100,000. This number exceeds the deaths from breast cancer, prostate cancer and AIDS combined.6
Although resistance to one or more antibiotics is widespread, nearly all bacteria are susceptible to at least one antibiotic. The challenge is identifying the appropriate antibiotic in a rapid, efficient manner. Current susceptibility testing methods require 2-4 days to return a result. Rapid antibiotic susceptibility testing has the potential to improve the treatment of infectious disease, reduce mortality, length of stay, and provider costs.
In a 400-bed metropolitan hospital in the Midwest, U.S.:
A patient presenting with suspected endocarditis is hospitalized and vancomycin is empirically prescribed. Prior to receipt of antibacterial therapy, blood cultures were drawn and sent to the microbiology laboratory. In light of the current hospital susceptibility patterns (68 percent rate of Methicillin-resistant S. aureus [MRSA]), vancomycin is an appropriate empirical choice.
After 3 days of vancomycin therapy, the patient's condition steadily worsened, with infection spreading to her spinal column and bones. The blood culture was positive within 12 hours (relatively early) and the Gram stain showed cocci in clusters, indicating Staphylococcus spp. The patient was continued on vancomycin and a standard broth dilution culture and susceptibility test was initiated.
Forty eight hours later, the pathogen was identified as methicillin-susceptible S. aureus (MSSA). Based upon this information, the patient was immediately switched from vancomycin to nafcillin. The change in therapy was associated with rapid response to the nafcillin with associated resolution of symptoms.
The attending physician presented this case at grand rounds. Had results confirming MSSA been available earlier, he would have changed therapy to nafcillin earlier. Nafcillin is associated with more rapid clinical response than vancomycin and more rapid initiation of this agent might have resulted in more rapid recovery and fewer complications.
This case illustrates several important points. First, in light of the fact that 68 percent of the S. aureus strains at his hospital were methicillin-resistant, vancomycin was an appropriate initial empirical choice.
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