Introduction
When the microorganisms do not respond to antibiotics, they are not killed and continue to proliferate. According to WHO (World Health Organization), infections acquired from multi-drug resistant bacteria contribute to 7,00,000 deaths, of which 2,00,000 are newborns. The common multi-drug resistant organisms are exclusively gram-negative bacilli, Staphylococcus aureus, and Enterococcus sp. These microorganisms are linked with relatively significant morbidity and mortality in the affected persons.
What Do Antibiotics Act Against?
Antibiotics are drugs that are specifically developed to target and kill bacteria. These do not act against infections caused by viruses like the common cold, flu, or sore throat. Antibiotic resistance means that these bacteria have changed their form such that they are no longer effective against antibiotics and are referred to as multi-drug resistant organisms.
Why Does Antibiotic Resistance Develop?
Antibiotic resistance develops due to the following reasons:
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The human body has numerous bacteria, of which few may be drug-resistant or turn resistant after exposure to an antibiotic.
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Antibiotic drugs usually kill the harmful bacteria that cause infection and illness but sometimes may kill good bacteria that offer protection from illness.
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These drug-resistant bacteria continue to dwell and proliferate inside the body and can pass their resistance ability to other bacteria as well.
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These drug-resistant bacteria, in turn, can cause infections.
How Are Infections by Antibiotic-Resistant Bacteria Different From Other Infections?
Antibiotic-resistant bacteria are different from other infections in the following ways:
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They are difficult and expensive to treat.
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Infections can last longer.
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Can make the child sick.
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Infections can be deadly at times.
How Do Antibiotics Work?
The two major works of antibiotics are:
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A bactericidal antibiotic kills the bacteria, such as Penicillin. These interrupt the formation of the cell wall by the bacteria or its contents.
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A bacteriostatic antibiotic inhibits the multiplication of bacteria.
Signs of improvement can be noticed only after a few hours or days after taking the antibiotic.
What Are the Reasons for Antibiotic Resistance in Children?
The reasons for antibiotic resistance in children are as follows:
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Overuse and Misuse of Antibiotics: Antibiotics are widely prescribed in children since they are exposed to a variety of infections, and they are more prone to acquiring these infections since their immune system is immature. Antibiotics are commonly prescribed incorrectly for infections caused by things other than bacteria, like viral infections. Improper use of antibiotics arises due to a poor understanding of the pathogens linked with various infections and the pharmacokinetic (movement of drugs in the body) and the pharmacodynamic (effect of drugs in the body) characteristics of the particular class of antibiotics.
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Correct Dosage: It is important to prescribe antibiotics to children appropriate to their age, needs, efficacy, safety, and dosage. Lack of specific pediatric clinical trials on antibiotics can often lead to antibiotic misuse, over or underuse, which can increase the risk of toxicity or pave the way for the emergence of antibiotic-resistant bacterial strains pertaining to the specific pediatric age group. The movement of drugs in the body (pharmacokinetics) varies and is complex in different pediatric age groups, from premature to newborns and from infants and children to teenage adolescents. The remarkable differences occur in neonates and infants.
The pharmacokinetics have to be kept in mind while prescribing antibiotics to neonates (newborns) and infants since kidney function varies extremely in the pediatric population and is age-dependent. More research on pediatric developmental physiology will enhance antibiotic prescription to children with greater safety, accuracy, and efficacy.
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Contraindicated Antibiotics: Certain antibiotics are contraindicated based on pediatric age, and this limits their usage to treat a range of bacterial infections. For example, fluoroquinolones are effective in treating various pediatric infections, but studies in young animals have revealed irreversible adverse effects on cartilage development, causing inflammation and derangement of weight-bearing joints. Another drawback of fluoroquinolones is their increased potential to cause resistance.
Another antibiotic that is contraindicated in children is tetracyclines since they cause tooth discoloration in children less than eight years of age and can also cause photosensitivity (sensitivity to light).
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Biofilms and Chronic Conditions: Biofilms are a group of bacteria that adhere to a particular surface. Biofilms can be found on damaged tissue or an implanted medical device. Biofilms and chronic conditions can cause microbial resistance in the following ways:
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Biofilms do not act aggressively and rather remain unresponsive to antibiotics for months or even years. They are rarely fatal.
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Biofilms are difficult to treat since they require a high dosage of antibiotics for a longer duration. Certain known mechanisms of antimicrobial resistance, like target mutations, modification of enzymes, and so on, do not offer protection from bacteria in biofilms.
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Three hypotheses can be put forth to explain the ineffectiveness of antibiotics in bacterial biofilms. The first hypothesis is that there is a slow or incomplete entry of the antibiotic into the biofilm. The second hypothesis is based on an alteration in the chemical microenvironment within the biofilm. The third hypothesis is the tolerance of certain bacteria within the biofilm as they differentiate into ‘persistor’ cells. Persistor cells have retarded or arrested growth and continue to proliferate even after severe stress. They cause recurrent bacterial infections.
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Children are excellent hosts of biofilms as they receive simple as well as complex medical devices like central venous catheters and heart defect patches. These medical devices create a favorable breeding environment for biofilms and bacteria and these remain unaffected by antibiotics. These persistent infections can be gotten rid of only through the replacement or removal of the device.
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Biofilms are common in the nasopharynx of children who are repeatedly affected by middle ear and upper airway infections. This explains the inefficacy of antibiotics in these children. Biofilms can also be found in children with chronic sinusitis.
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Chronic health conditions like cystic fibrosis (a hereditary disorder that affects the lungs, pancreas, liver, kidneys, and intestine) are linked with morbidity and mortality. Both acute and chronic infections occur persistently because of the pathophysiology or due to frequent and long hospitalizations. Pediatric patients with cystic fibrosis are more susceptible to opportunistic infections than adults.
How to Overcome Antibiotic Resistance in Children?
Antibiotic resistance in children can be overcome in the following ways:
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Antimicrobial Stewardship: Antimicrobial stewardship is the coordinated intervention that is specifically developed to improve and measure the appropriate usage of antibiotics by ensuring proper selection of the drug which includes the dosage, duration, and route of administration. This can be done by a team of healthcare professionals by providing knowledge about the use of antibiotics and also through educational interventions.
The local antimicrobial prescriptions should be audited and reviewed regularly. The dosage should be prescribed keeping in mind the age and the physiological developmental processes of the child. Precise dosing in children is extremely important.
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Correct Diagnosis: About half of the antibiotic therapies are initiated without a correct identification of the causative agent. An accurate antimicrobial susceptibility testing (AST) is necessary to avoid the spread of antimicrobial resistance and to select the correct antibiotic that will act against the infection.
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Development of New Antibiotics: New antibiotics suitable for pediatric use have been approved that act against multi-drug resistant pathogens. These drugs include Ceftaroline, Ceftazidime/Avibactam, Ceftolozane/Tazobactam, Tedizolid, and Dalbavancin. More clinical studies are required on the above data. Specific pharmacokinetic trials also have to be carried out to predict the best dosage for specific pediatric age groups rather than determining it from adult dosages.
How Can Parents Help With Antibiotic Resistance in Children?
Parents can help prevent antibiotic resistance in their children in the following ways:
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Antibiotics should not be given for colds, flu, sore throat that is not caused by streptococcus, and runny nose as these are viral infections.
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Consult the pediatrician (child specialist) about whether the child will require antibiotics or not. Pediatricians should not be pressed to give antibiotics as they know what is best for the child.
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The pediatrician may suggest ‘wait and watch’ before starting antibiotics.
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Possible side effects of antibiotics should be discussed with the pediatrician.
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Leftover antibiotics should be discarded based on the doctor's instructions.
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Antibiotics should not be stocked for future use. Antibiotics prescribed for other children should not be used, and one must not share antibiotics with other children without the doctor’s knowledge.
Conclusion
Antibiotic resistance has become a worldwide threat and is putting children at risk. Inappropriate use, over and underuse of antibiotics, and incorrect diagnosis are increasing the emergence of multi-drug resistant pathogens. This can be overcome by developing software that can determine the age-appropriate dosage, awareness among clinical teams regarding the proper prescription of antibiotics, use of antimicrobial susceptibility tests, and promote the use of new antibiotics that act against multi-drug resistant pathogens. Parents must also avoid the unnecessary use of antibiotics for their children and must consult a pediatrician in case of any illness.
