**2.1 Antibiotic misuse**

Perhaps the most commonly known cause of the development of antibiotic resistance is the so-called misuse of antibiotics. This phrase refers not only to the patient's adherence to antibiotic prescription instructions, but also to the doctors that prescribe antibiotics unnecessarily. Many times problems with over prescription of antibiotics comes from the patients demand. Perhaps doctors are concerned with patient satisfaction or wish to decrease the likelihood of a follow up visit for a viral illness which could result in a bacterial infection. It is possible that the patients have developed an expectation to leave the doctor's office with prescription in hand. Regardless of the reason, antibiotics administered for

(Christensen et al., 2009; Lynch et al., 2009; Morbidity and Mortality Weekly Report [MMWR], 2009; Phares et al., 2008; Robinson et al., 2001; Tanaka et al., 2003)*.* Although in some of these cases antibiotic resistance is already observed, they are included primarily because of the availability of case reports with these diseases. Figure 2 represents a comparison of total reported cases of Streptococcal disease, invasive, group A to those that were drug resistant in the United States from 2002 to 2007. The percentage of cases that showed drug resistance are shown for each year. These data do not suggest a large increase in the number of reported cases but a trend of increasing resistance. Also, infections caused by these bacteria exhibit characteristics and trends similar to those

Fig. 2. The total number of *Streptococcal* disease (invasive, group A) cases reported in the United States between 2002 and 2007 compared to the number of cases that demonstrated drug-resistance (shown as a percentage each year.) Data were compiled by the authors from

Perhaps the most commonly known cause of the development of antibiotic resistance is the so-called misuse of antibiotics. This phrase refers not only to the patient's adherence to antibiotic prescription instructions, but also to the doctors that prescribe antibiotics unnecessarily. Many times problems with over prescription of antibiotics comes from the patients demand. Perhaps doctors are concerned with patient satisfaction or wish to decrease the likelihood of a follow up visit for a viral illness which could result in a bacterial infection. It is possible that the patients have developed an expectation to leave the doctor's office with prescription in hand. Regardless of the reason, antibiotics administered for

the Center for Disease Control Morbidity and Mortality Weekly Reports, 2002-2007.

bacterium that have been placed on the AATF list.

**2. How did bugs become "super?"** 

**2.1 Antibiotic misuse** 

unnecessary purposes, including non-bacterial infections and prophylaxis, encourage the development and the spread of antibiotic resistance. Considering one study that estimated over 90% of all infections are viral, yet over half the US patients are taking antibiotics for these viral infections (*Science Daily*, 2005).

A study published in *Science* in 2010 utilized a genomic approach to examine single nucleotide polymorphisms using a high resolution second generation DNA sequencing platform. Researchers examined two samples: one was a global collection ranging from 1982 to 2003 and the second was a collection from Thailand over a seven month period. Sample one represents a random population while the second samples are limited to a single transmission. The data suggests specific European samples from the global collection relate to those collected from the Thailand hospital. The complete set of data allowed phylogenic analysis and an estimation of time since the evolution of the resistance. The researchers observed that 28.9% of the homoplasies identified had direct links to current therapeutics, providing strong evidence that the misuse of antibiotics in today's medical practice is a major contributor to the development of resistance. Furthermore, this study has allowed an estimate of one single nucleotide polymorphism every six weeks, an essentially unimaginable rate in evolutionary time (Harris et al., 2010).

The second part of this concern is patient adherence. This usually stems from the fact that antibiotic treatment, assuming it is a non-resistant bug, usually improves clinical symptoms within 1 to 3 days. Patients have difficulty continuing to take the prescription when their symptoms have been alleviated. They also have a tendency to "save" the rest of the prescription in case they need it again in the future. The contribution of this action to antibiotic resistance is simple: initial treatment kills most of the bacteria, particularly those susceptible to the antibiotic; those with some minor susceptibility to the antibiotic survive and thrive as the dosing is waned. Essentially this is an acceleration of "survival of the fittest." Bacteria that have been able to survive, reproduce and pass along whatever genetic variance they carry which provides resistance.

Recent reports have warned the overuse of antibiotics as prophylaxis in the food industry, although there is some controversy over the actual contribution to food animal antibiotic administration to the growing problem of global "superbug" problems (Singer et al., 2003). It is proposed that unnecessary use of antibiotics in food animals will contribute to resistance in the same ways as over prescribing and lack of adherence in the human population.
