INTRODUCTION
The emergence of antibiotic resistance is increasing and becoming a big problem either nationally or globally. The magnitudes of problems tend to rise as there are numerous factors, either coming from bacteria or human, which can facilitate the development of resistance. This essay will examine problems related to antibiotic resistance, factors contributing the development of antibiotic resistance, mechanism of drug resistance in bacteria and potential solutions of antibiotic resistance.
THE PROBLEMS RELATED TO ANTIBIOTIC RESISTANCE
A direct consequence of antibiotic resistance is a failure of therapy since bacteria are not sensitive anymore to the antibiotics. Factors which may indicate the failure of treatment are longer stay of patients in a hospital and progression of the disease even lead to a death. Moreover, the treatment failures can give a burden to the patients and society since they have to spend more money due to prolonged hospital stay, additional diagnostic or therapeutic procedures, and additional antibiotic use. Infection caused by resistant pathogen can also indirectly cause loss of productivity, long-term disability and excess mortality (Grundman, et al., 2006; Howard et al., 2003; Larson, 2007). A meta-analysis study has been conducted by Cosgrove et al. (2003) showed that MRSA (methicillin-resistant Staphylococcus aureus) bacteremia has an impact on significant increase of mortality compare to MSSA (methicillin-sensitive Staphylococcus aureus) bacteremia. Vancomycin-resistant enterococci (VRE) bacteremia also causes prolonged hospitalization among debilitated patients and higher medical cost (Stosor and Postelnick, 1998). Indeed, antibiotic resistance poses problems of higher morbidity and mortality, extra hospitalization, and higher medical expenses to patients and society.
MRSA AND VRE
Some bacteria which have developed resistance to antibiotics and becoming important causes of health-care associated infections and a public health concern are MRSA and VRE. MRSA, which arose in the 1960s, classically causes health-care associated infections. According to Baba et al. (2002), in the past 5 years, MRSA infections have been recognized in the community and affected people lack traditional risk factors for instance long-term hospital stay or surgery. MRSA is also becoming evident in home nursing (Nikaido, 2009).
Community-acquired MRSA (CA-MRSA) infection can cause severe and fatal infections even in healthy individuals. CA-MRSA typically affects children and young adults (Baba et al., 2002). Community-acquired MRSA has been isolated from children and adults with skin and soft tissue infections, septic arthritis, toxic shock syndrome, and necrotizing pneumonia (Grundman, et al., 2006). Individuals who might have higher risk of getting CA-MRSA infections are, for example, men who have sex with men and children in day care (Grundman, et al., 2006). Higher mortality also happens in infections caused by VRE. According to Stosor (1998), infection with VRE will increase a risk of patient’s death.
Additionally, both MRSA and VRE are not merely resistant to a single antibiotic;
MRSA are not only resistant to methicillin but usually also to aminoglycosides, macrolides, tetracycline, and lincosamides. VRE frequently express additional resistance to multiple antibiotics, including ampicillin and aminoglycosides (Schouten et al., 2000) This heteroresistance can make detection of organisms are difficult in clinical laboratory. Therefore, MRSA and VRE infections become a problem not only in a clinical setting but also in the community due to its high virulence and multi resistant trait.
THE MECHANISMS OF RESISTANCE
A variety of mechanisms are performed to build resistance in bacteria. Different bacteria have different mechanisms and even in one species, they have more than one mechanism of resistance. In general, bacteria can defend from antibiotics by inactivating the antibiotic through enzymatic inactivation (for example by beta lactamase produced by Gram negative rods to inactivate beta lactam antibiotics), changing the porins (for example, in Pseudomonas sp to resist imipenem, changing the target of antibiotic (for example altering penicillin binding protein by MRSA) and conferring efflux systems to pump antibiotics out of cell (for example in streptococci) (Rice and Bonomo, 2007)
MUTATION AND TRANSFORMATION AS DETERMINANTS OF RESISTANCE
The development of antibiotic resistance is favoured by factors coming from bacteria and factors relating to human behaviour. In terms of evolution, resistance to antimicrobial drugs is a particular aspect of general evolution of bacteria which can not be halted by human (Courvalin, 2005). Mutation of regulatory genes is an important factor causing bacteria to be resistant. For example, resistance to rifampin is accomplished by mutation in RNA polymerase gene (rpoB) because rifampin targets the cellular RNA polymerase (Rice and Bonomo, 2007).
If resistance can not be ascertained by mutation, the susceptible pathogens have to find and acquire the resistance genes through gene exchange (Courvalin, 2005; Martinez and Baquero, 2002). The transformation of resistance determinants can occur naturally, referring absorption of naked DNA from the environment under the appropriate situation, but most of bacteria are incompetent of natural transformation, therefore other mechanisms are achieved to acquire the resistance genes. General machinery used to transfer the resistance gene is plasmid. Plasmids are major vectors for spreading antibiotic resistance genes and other virulence determinants among bacterial population. Other means of exchanging the genes are bacteriophages and transposon (Martinez and Baquero, 2002; Rice and Bonomo, 2007). The accurate source of resistance genes is difficult to determine, although in some cases the genes are coming from outside the genus (Rice and Bonomo, 2007).
HUMAN BEHAVIOUR AND DEVELOPMENT OF RESISTANCE
The imprudent use of antibiotic in human and non human niches can facilitate the development of antibiotic resistance. According to Larson (2007) and Orzech and Nichter (2008), several practices in antibiotic use which contribute to the emergence of antibiotic resistance are the inappropriate use of antibiotics for viral infection and the use of antibiotics as a long-term prophylactic therapy. The irrational use of antibiotic and the use of broad spectrum antibiotic can lead to selective pressure condition which eventually select resistant strains to grow. Then, the resistant strain can spread and colonize other individuals (Courvalin, 2005; Orzech and Nichter, 2008). Indeed, the overuse and misuse of antibiotic in human are still contributing to the emergence of drug resistance.
Admittedly, the indiscriminate use of antibiotics in animal husbandry and agriculture also play a role in developing resistance (Larson, 2007). According to Ena et al. (1998) cited in Rice and Bonomo (2007), a correlation between high rates of ciprofloxacin resistance in E. coli and the use of fluoroquinolones in poultry has been established. The emergence of VRE (Vancomycin-resistant enterococci) with vanA gene was proven to be related with the use of avoparcin, a glycopeptide antibiotic, to promote growth of animals (Rice and Bonomo, 2007; Wegener, 2005 cited in Orzech and Nichter, 2008). The gene pool of antibiotic in nature world can spread out because of the use of antibiotics in animal food (Madigan, et al., 2000). Consequently, human colonization and sometimes severe infection with the same or associated drug-resistant strains can happen as a result of exposure (either directly or through food chain) to animals that have been fed with antibiotics (Larson, 2007; Madigan, et al., 2000). The use of antibiotic in crops also plays a part of antibiotic resistance. The non pathogenic orchard bacteria and plant pathogens developed acquired tetracycline resistance and streptomycin resistance, respectively.
Another factor of development of antibiotic resistant is an insufficient control of infection which can spread the resistant pathogen from one source to another, for example, poor hand washing procedure among health care workers and contaminated equipments in a hospital can be a source of infection particularly to immunocompromised patients. Patients of high risk condition such as those who are in a post operative period are more likely having colonization with MRSA (Larson, 2007; Perl et al., 2002 cited in Rice and Bonomo, 2007 p 1116).
MEASURES AND POSSIBLE SOLUTIONS
Some measures aimed to slow the emergence of resistance should be based on the mentioned determinants of the resistance. According to Centre for Disease Control or CDC (2004), generally, in healthcare setting several actions can be carried out to prevent antibiotic resistance namely prevent of infection (including vaccination and use medical devices wisely) and use antibiotics prudently. In relation to Orzech and Nichter (2008), judicious use of antibiotics including minimize use of broad spectrum antibiotics, treat infection not colonization, prescribe shorter treatment of antibiotics, and use combination of antibiotics. In addition, prevent transmission of pathogen is also an important measure, including comply with hand washing procedure, and do surveillance of carriers of antibiotic-resistant pathogen (CDC, 2004). In addition, from public health perspective, it is imperative to educate patients to use antibiotics properly, and to educate doctors to prescribe antibiotics wisely. Restricted use of antibiotics in animals and plants is also encouraged because such regulation can decrease antibiotic resistance in animals and humans (Larson, 2007; Ozrech and Nichter, 2008). Drug resistance will always happen in spite of the rational use of antibiotics because it is part of bacterial evolution toward their pathogenicity. Therefore, the development of new more potent antibiotics is mandatory (Larson, 2007). Evolutionary solutions is suggested by Ozrech and Nichter (2008) to turn bacteria against themselves by seeking techniques to make resistant pathogenic bacteria can not survive longer in their environment. This less fitness will decrease the progression of the infection.
CONCLUSION
To conclude, antibiotic resistance can bring a serious problem both to clinical and public health setting and the causes are multifactorial. The successful efforts in preventing the dissemination of resistance are determined by bacterial factors and factors related to human behaviour in using antibiotics. Although the resistance itself can not be stopped, human can decrease the spread of gene resistant of pathogenic bacteria.
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