Using in-vitro models to analyse the efficacy of antibiotics such as fluoroquinolones is not a novel idea. Various systems can be used to mimic the pharmacokinetic profiles in-vivo in order to simulate drug clearance.
The relationship between concentration or exposure and bactericidal effects can then be described in order to calculate dosing regimens and pharmacodynamic values such as the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC). MIC is defined as the minimum concentration of antibacterial agent that inhibits pathogen growth in-vitro. The MIC is commonly used to measure changing antibiotic resistance in bacterial strains and, as such is widely understood. Minimum bactericidal concentration (MBC) is defined as the minimum concentration of antibiotic that kills a pathogen in-vitro.
There are clear advantages and disadvantages to in-vivo studies such as lower costs, greater degree of control, wider dose ranges, evaluation against a broader selection of bacterial species and ability to mimic human conditions. Overuse of antibiotics has led to a shift in the application of in-vitro pharmacodynamic models from focusing on antibiotic effect, to focusing on prevention of resistance. The rapid rise of Staphylococcus aureus resistance to fluoroquinolones such as ciprofloxacin is a fantastic example of evolution in action. In 2004 up to 89% of S. aureus isolates were resistant to ciprofloxacin in some parts of the world(Oonishi et al., 2007). In-vitro methods are now being used to calculate optimum dosage regimes in order to help restrict bacterial resistance to antibiotics and preserve the effectiveness of existing drugs.
Background
The treatment of infectious diseases drastically changed in 1928 with the discovery of penicillin. Diseases virtually equivalent to a death sentence have since become manageable using anti-infectives. Traditionally broad spectrum antibiotics such as the synthetic family of fluoroquinolones were readily prescribed for a large range of infections. However, it was apparent that bacteria rapidly developed resistance to this class and other classes of antibiotics (Linder et al., 2005).
With continued use of antibiotics, resistant bacterial strains have emerged, such as methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci. According to the US Center for disease control, of 2 million patients infected annually in US hospitals, 1.4 million of these infections are resistant to one or more drugs resulting in the death of around 90,000 people per year. Whilst MRSA was found originally in hospitals, more patients are now presenting at hospitals with antibiotic-resistant bacteria acquired externally (Patel et al., 2008).
Studies on antibiotic resistant infections have suggested that in comparison to susceptible infections, morbidity, mortality and costs of treatment are increased(Kollef et al., 2000). You might think that new drugs coming onto the market may be sufficient to safeguard against the rise of resistance to existing drugs. However the rate of resistance is rising alarmingly faster than the rate at which new drugs are being introduced. Growth in sales is flat and falling in some markets.
The worldwide market for antibacterial drugs accounting for roughly half of the anti-infective market was $24.5 billion in 2009, only 0.7% greater than 2008. Although these circumstances may drive some forward to invest in new drug development, other investors are reluctant. Therefore it is essential that in order to protect public health, research is carried out on how to best preserve and prolong the efficacy of existing antibiotics. (Chung et al., 2006)(Kalorama Information, 2nd October 2009)
One strategy to prolong the efficacy of existing antibiotics has been the implementation of guidelines and recommendations on the appropriate use of antibiotics with positive results. For example in Finland, Pestotnik et al introduced automated guidelines for antibiotic use into clinical practice and showed a stabilization of resistance patterns locally, reduced mortality from3.65% to 2.65%, a 22.8% decrease in antibiotic use over 7 years, and a cost reduction from $122.66/patient in 1988 to $51.90/patient in 1994(Pestotnik et al., 1996).
Another strategy to protect the efficacy of existing antibiotics involves in-vitro pharmacodynamic models designed to better understand development of resistance and how it can be stopped.
Clare Jackson - Clare enjoys research and has a range of interests. With a background in scientific writing she likes to include lots of information in ...
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