|Year : 2014 | Volume
| Issue : 1 | Page : 1-5
Preventing bacterial infections in the society: Lessons to be learnt
Gajanan S Gaude
Department of Respiratory Medicine, KLE University's Jawaharlal Nehru Medical College, Belgaum, Karnataka, India
|Date of Web Publication||2-Jul-2014|
Gajanan S Gaude
Department of Respiratory Medicine, KLE University's Jawaharlal Nehru Medical College, Belgaum, Karnataka
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Gaude GS. Preventing bacterial infections in the society: Lessons to be learnt. Indian J Health Sci Biomed Res 2014;7:1-5
Antibiotics and similar drugs, together called antimicrobial agents, have been used for the last 70 years to treat patients who have infectious diseases. Since the 1940s, these drugs have greatly reduced illness and deaths from infectious diseases. Antibiotic use has been beneficial, and when prescribed and taken correctly, their value in patient care is enormous. However, these drugs have been used so widely and for so long that the infectious organisms the antibiotics are designed to kill have adapted to them, and thus, making the drugs less effective. Antibiotic resistant bacteria are bacteria that are not controlled or killed by antibiotics. They are able to survive and even multiply in the presence of an antibiotic. Bacteria that are resistant to many antibiotics are known as multi-resistant organisms (MROs). People infected with antimicrobial-resistant organisms are more likely to have longer, more expensive hospital stays, and may be more likely to die as a result of the infection. In the past 60 years, antibiotics have been critical in the fight against infectious disease caused by bacteria and other microbes. Antimicrobial chemotherapy has been a leading cause for the dramatic rise of average life expectancy in the 20 th century. However, disease-causing microbes that have become resistant to antibiotic drug therapy are an increasing public health problem. One part of the problem is that bacteria and other microbes that cause infections are remarkably resilient and have developed several ways to resist antibiotics and other antimicrobial drugs. This happens mainly due to increasing usage, and misuse, of existing antibiotics in a variety of medical illnesses even if it is not indicated.  Nowadays, about 70% of the bacteria that cause infections in hospitals are resistant to at least one of the drugs most commonly used for treatment. An alarming increase in resistance of bacteria that cause community acquired infections has also been documented, especially, in the staphylococci and pneumococci (Streptococcus pneumonia), which are prevalent causes of disease and mortality. Antimicrobial resistance, a global problem, is particularly pressing in developing countries where the infectious disease burden is high and cost constrains the replacement of older antibiotics with newer, more expensive ones. Management of common and lethal bacterial infections has been critically compromised by the appearance and rapid spread of antibiotic-resistant bacteria. In a recent study,  25% of bacterial pneumonia cases were shown to be resistant to penicillin, and an additional 25% of cases were resistant to more than one antibiotic. Urinary tract infections (UTIs) are amongst the most common infections encountered in the clinical practice. The most common pathogen involved in UTIs is the Escherichia coli, being the principal pathogen both in the community as well as in the hospital. The bacterial resistance to various antibiotics for this pathogen is on the rise, with a recent study from Puducherry  reporting high prevalence of bacterial resistance to various pathogens such as E. coli, Pseudomonas, Proteus, Klebsiella, and Acinetobacter. Another important finding was that the resistance was high to various antibiotics including, some of the newer antibiotics, which is of concern to the treating clinicians. 
Evidence also began to accumulate that bacteria could pass genes for drug resistance between strains and even between species. For example, antibiotic-resistance genes of staphylococci are carried on plasmids that can be exchanged with bacillus, streptococcus, and Enterococcus providing the means for acquiring additional genes and gene combinations. Some of the genes are carried on transposons, segments of DNA that can exist either in the chromosome or in plasmids. In any case, it is clear that genes for antibiotic resistance can be exchanged between strains and species of bacteria by means of the processes of horizontal gene transmission. Some of the most important types of MROs that have been encountered include: Methicillin/oxacillin-resistant Staphylococcus aureus (MRSA) vancomycin-resistant enterococci (VRE) extended-spectrum beta-lactamases (ESBLs) (which are resistant to cephalosporins and monobactams), and penicillin-resistant S. pneumonia (PRSP) MRSA and VRE are the most commonly encountered multiple drug resistant organisms in patients residing in nonhospital health-care facilities, such as nursing homes and other long-term care facilities. PRSP are more common in patients seeking care in out-patient settings such as physician's offices and clinics, especially, in pediatric settings. ESBLs are most often encountered in the hospital (intensive-care) setting, but MRSA and VRE also have significant nosocomial ecology. The ESBL enzymes are plasmid mediated enzymes capable of hydrolyzing and inactivating a wide variety of beta lactams, including, third generation cephalosporins, penicillins, and aztreonam. These enzymes are the result of mutations of temoniera enzymes (TEM)-1 and TEM-2 and sulfhydryl variable enzymes (SHV-1). All these beta-lactamases enzymes are commonly found in the Enterobacteriacea family. Normally, TEM-1, TEM-2, and SHV-1 enzymes confer high level resistance to first generation cephalosporins. Widespread use of cephalosporins and aztreoman is believed to be a major cause of mutations in these enzymes that has led to the emergence of the ESBLs. There are various Enterobacteriaceae species; however, majorities of ESBL producing strains are Klebsiella pneumonia, Klebsiella oxytoca, and E. coli. Other organisms reported to harbor ESBLs include Enterobacter sp., Salmonella sp., Morganella morganii, Proteus mirabilis, Serratia marcescens, and Pseudomonas aeruginosa. However, the frequency of ESBL production in these organisms is low.
Respiratory infections remain one of the important causes of morbidity and mortality in the world today and the need for effective antimicrobial agent is as pressing now as at any time. The safety and efficacy of beta-lactam antibiotics has established the importance of this class of antibacterial agents for the therapy of many bacterial infections. Thus, benzylpenicillin, or one of the first choice for the treatment of infections caused by Gram-positive cocci and a beta-lactam antibiotic is frequently preferred for the treatment of infections caused by Gram-negative bacteria. In recent years, the number of new cephalosporins and novel beta lactams such as cephamycins, oxacephams, and the carbapenems in clinical use has increased rapidly; however, widespread usage has resulted in the selection of bacterial variants resistant to some or all of the beta lactam agents currently available. The success of the penicillanase-stable penicillins in the therapy of infections caused by penicillin-resistant staphylococci has been accompanied by the emergence of MRSA as a major problem. These strains existed before the development of the semi-synthetic penicillins, but the frequency of isolation has increased significantly, and in many hospitals epidemic of MRSA infections have become difficult to control. Many strains of MRSA are susceptible only to vancomycin, and there is a vital need for the new drugs active against MRSA in light of the potential for the possible spread of vancomycin-resistance from enterococci to staphylococci. Unless, antibiotic resistance problems are detected as they emerge, and actions are taken immediately to contain them, society could be faced with previously treatable diseases that have become again untreatable, as in the days before antibiotics were developed. Highly resistant pathogens are a major cause of excess mortality among patients with community- and hospital-acquired pneumonia. In the hospital setting, major risk-factors for infection with resistant pathogens include extended hospitalization, mechanical ventilation, and inadequate initial antibiotic therapy. 
Bacteria can become "resistant" to individual antibiotics by developing specific defense-mechanisms, which make the antibiotic ineffective. Generally, there are three mechanisms that are utilized by bacteria to develop resistance:  (1) Preventing the antibiotic from binding with and entering the organism, (2) producing an enzyme that inactivates the antibiotic, or (3) changing the internal binding site of the antibiotic. One-way in which bacteria have become resistant to beta-lactam antibiotics is by being able to express beta-lactamase enzymes - an example of the second type of resistance. There are actually dozens of enzymes, produced by many different bacteria, which are capable of degrading the beta-lactam structured antibiotics. The TEM-1 enzyme, capable of degrading ampicillin emerged about 40 years ago. This enzyme has since evolved leading to roughly, 128 different TEM beta-lactamases; some with activity against almost all beta-lactams. Other important classes of beta-lactamases are SHV, Pseudomonas specific enzymes, and oxacillnases enzymes and a similar evolution can be observed in these classes. In addition, chromosomal amp beta-lactamases have relocated into plasmids and emerged in different pathogenic species where they cause resistance to virtually all beta-lactams. Of even greater concern is the worldwide emergence of the increasing number of isolates of S. pneumonia with reduced susceptibility to penicillins and cephalosporins. At present, level of resistance to beta-lactam of many isolates is comparatively low, and penicillins and cephalosporins can often be prescribed, possibly at higher dosage. Furthermore, the transfer of antibiotic resistance genes between staphylococci, enterococci, and streptococci leading to acquisition of staphylococcal beta-lactamase by enterococcci raised the possibility of the spread the enzyme to other streptococci, including the pneumococcus.
The discovery that beta-lactamase mediated resistance to penicillins and cephalosporins could be transmitted among enteric bacterial population as whole, one that has largely fulfilled by the dissemination of plasmid-mediated beta-lactamase amongst many Gram-negative bacteria. It has been also observed that extensive usage of the third generation cepahlosporins has resulted in the emergence in-hospital of resistant strains of Gram-negative bacteria possessing beta-lactamase capable of hydrolyzing the antibiotics in question. Bacteria possessing plasmid-mediated ESBL are comparatively uncommon, but the development of oral derivatives and widespread usage in both community and the hospital could well see the spread of these novel enzymes. The other area in which the usage of second and third generation cepharosporins has created significant therapeutic problems is the selection of the highly resistant strains of important nososcomial pathogens, such as Enterobacter, Pseudomonas, and Serratia species. 
| Inappropriate Use of Antibiotics in the Medical Environment|| |
One problem is the casual use of antibiotics in medical situations where they are of no value. This is the fault of both health-care workers and patients. Prescribers sometimes thoughtlessly prescribe "informed" - demanding patients with antibiotics. This leads to use of antibiotics in circumstances where they are of not needed, e.g. viral upper respiratory infections such as cold and flu, except when there is a serious threat of secondary bacterial infection. Another problem is patient failure to adhere to regimens for prescribed antibiotics. Patients and doctors need to realize their responsibility when they begin an antibiotic regimen to combat an infectious disease. There are several measures that should be considered: Patients should not take antibiotics for which there is no medical value (corollary: Doctors should not prescribe antibiotics for which there is no medical value); patients should adhere to appropriate prescribing guidelines and take antibiotics until they have finished; patients should be give combinations of antibiotics, when necessary, to minimize the development of resistance to a single antibiotic; patients need to be given another antibiotic or combination of antibiotics if the first is not working.
| Combating Bacterial Resistance|| |
Use the right antibiotic in an infectious situation as determined by antibiotic sensitivity testing, when possible. One should stop unnecessary antibiotic prescriptions. Unnecessary antibiotic prescriptions have been identified as causes for an enhanced rate of antibiotics resistance development. Unnecessary prescriptions of antibiotics are made when antibiotics are prescribed for viral infections (antibiotics have no effect on viruses). This gives the opportunity for indigenous bacteria (normal flora) to acquire resistance that can be passed on to pathogens. One should finish antibiotic prescriptions for the full period. Unfinished antibiotic prescriptions may leave some bacteria alive or may expose them to sub-inhibitory concentrations of antibiotics for a prolonged period of time.
Appropriate antibiotic selection by physicians can be aided by the adoption of rapid diagnostic methods, which will become increasingly available and should encourage a more rational choice of narrow spectrum antibiotics.  Much nosocomial infection in the hospital is due to the extensive use of indwelling lines and catheters required by the technological advances in medicine, better hygienic practice, and the use of specific topical antibacterial agents and the introduction of material resistant to bacterial adhesion in the incidence of bacteremic episodes due to antibiotic resistant bacteria. Avoidance of unnecessary prolonged antibiotic use can help prevent the development of resistance. Early initiation of treatment with an appropriate empiric antibiotic, followed by an antibiotic that specifically targets pathogens identified following gram stain and culture results with a defined course of therapy plays a major part in improving outcomes and reducing the risk of resistance. Clinicians who manage patients with both community-acquired and hospital-acquired pneumonia need to be aware of the predominant pathogens in their institutions and the level of local in vitro antibiotic susceptibility. Institutions with endemic ESBL-producing organisms need to determine whether there is a high-rate of cephalosporins usage, especially, third generation cephalosporins. Several studies have shown that by limiting the use of these agents alone or in combination with infection control measures, the frequency of ESBL isolates can be reduced substantially. The development of specific vaccines, rendered more effectively by advances in genetic engineering, provides another approach. 
The Center for Disease Control,  in a campaign to prevent antimicrobial resistance in health-care settings, has elucidated the following 12 steps: Vaccination; get the catheters out, target the pathogen, access the experts, practice antimicrobial control; use local data, treat infection, not contamination, treat infection, not colonization, know when to say no to vancomycin, stop antimicrobial treatment, isolate the pathogen, and break the chain of contagion.
The national guidelines should be formulated and implemented for the correct and effective use of antibiotics in clinical practice to combat the bacterial resistance. Every hospital should have the antibiotics committee that should formulate the antibiotic guidelines by taking into consideration the local antibiotics resistance patterns. Hence, a close cooperation should exist between the microbiologist and the clinicians. The guidelines should be based on the systematic review of the scientific data. The committee should identify evidence that is lacking and areas for further research. The guidelines should be reviewed by respected peers who are not members of guideline panel; however, who are experts in the relevant field. Guidelines should not be static. They should be reviewed at periodic intervals that should be specified, and updated to take account of advances in medical knowledge, changes in clinical practice and local circumstances, and outcome of guideline evaluations. 
| Ways to Prevent Antibiotic Resistance|| |
The most important ways to prevent antibiotic resistance are: Minimize unnecessary prescribing and overprescribing of antibiotics. This occurs when people expect doctors to prescribe antibiotics for a viral illness (antibiotics do not work against viruses) or when antibiotics are prescribed for conditions that do not require them; complete the entire course of the prescribed antibiotic so that it can be fully effective and not breed resistance; and practice good hygiene and use appropriate infection control procedures.
| Standard Precautions For Healthcare Facilities|| |
Standard precautions are work practices that provide a basic level of infection control for the care of all patients, regardless of their diagnosis or presumed infection status. These precautions should be followed in all healthcare facilities and include: Good personal hygiene, such as hand washing before and after patient contact and the appropriate use of alcohol-based hand rub solutions; the use of barrier equipment such as gloves, gowns, masks and goggles; appropriate handling and disposal of sharps (for example, needles) and clinical waste (waste generated during patient care); and strictly following aseptic techniques. Implementing standard precautions minimizes the risk of transmission of infection from person to person, even in high-risk situations.
Antimicrobial stewardship is the ongoing effort by a health-care institution to optimize antimicrobial use among hospitalized patients to improve patient outcomes, ensure cost effective therapy and reduce the emergence of antibiotic resistance. Educating clinicians is of paramount importance as they need to understand that prescribing an antibiotic to a patient does not only affect the patient but has an impact on the bacterial flora of the hospital. Formulary restriction is a method of restricting the use of high-end antibiotics, such that they can only be prescribed post-authorization by an infectious diseases specialist. The program needs to be spearheaded by the antimicrobial management team, which is a multi-disciplinary team consisting of a microbiologist, infectious diseases specialist and antibiotic pharmacist.  This group should audit the use of antibiotics, perform surveillance of resistance data and provide a timely feedback to clinical teams. Dose optimization, de-escalation changing the route of administration from intravenous to oral in a timely manner and implementing care pathways form part of the scope of activities of this team.
Two complementary types of surveillance are recommended: Surveillance for antibiotic resistance and surveillance for antibiotic use. This supports a recommendation made in the national policy document. By itself, surveillance of any type will not change antibiotic use or the spread of resistant organisms; however, knowing resistance levels and tracking them over time is a powerful tool to support real changes. Once the link between resistance and antibiotic use is accepted, tracking antibiotic use can be used as a surrogate for changes in resistance patterns.
Antibiotic resistance in a variety of common respiratory pathogens continues to be a problem. Vigilance for patients at risk for developing resistance is key, along with fastidious infection control measures and appropriate use of antibiotics. Antimicrobial resistance is here to stay. In evaluating bacterial resistance, it may be naive to anticipate reaching a grand control over resistance. The hope perhaps lies in slowing down development of newer resistance while continuing to develop new agents at a rate sufficient to keep ahead of bacteria.
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