When should antibiotics be prescribed for children. How do antibiotics differ from other medications. What are the potential side effects of antibiotic use in children. Why aren’t antibiotics always the right treatment for colds and ear infections. How can parents distinguish between viral and bacterial infections in their children.

Understanding Antibiotics: Their Role and Limitations in Treating Childhood Illnesses

Antibiotics are powerful medications designed to combat bacterial infections. However, their effectiveness is limited to specific types of illnesses, and misuse can lead to potential harm. Parents often have questions about when and how antibiotics should be used for their children’s health concerns. This comprehensive guide aims to address these questions and provide clarity on the appropriate use of antibiotics in pediatric care.

What Are Antibiotics and How Do They Work?

Antibiotics are medications that target and eliminate bacteria causing infections in the body. They work by either killing the bacteria directly or preventing their growth and reproduction. However, it’s crucial to understand that antibiotics are ineffective against viral infections, which cause many common childhood illnesses.

The Importance of Proper Antibiotic Use

Using antibiotics when they are not necessary can have negative consequences. Overuse or misuse of antibiotics can lead to antibiotic resistance, where bacteria evolve to become less susceptible to these medications. This makes future infections more difficult to treat. Additionally, like all medications, antibiotics can cause side effects that may be uncomfortable or potentially harmful to your child.

Common Misconceptions About Antibiotics in Pediatric Care

Many parents have misconceptions about when antibiotics should be used. Let’s address some of the most common questions and clarify these misunderstandings.

Can Antibiotics Treat Colds?

Colds are almost always caused by viruses, not bacteria. Antibiotics are ineffective against viral infections and will not help your child recover from a cold faster. Most cold symptoms, such as runny nose, cough, and congestion, will improve on their own without any medication.

It’s worth noting that young children, especially those in daycare settings, can experience 6 to 8 colds per year. This is normal and does not necessarily indicate a need for antibiotic treatment.

Do Colds Always Turn into Bacterial Infections?

Contrary to popular belief, bacterial infections rarely follow viral infections. Prescribing antibiotics for viral infections in hopes of preventing bacterial infections is not an effective strategy. In fact, this approach may lead to unnecessary side effects such as diarrhea.

Is Colored Mucus a Sign of Bacterial Infection?

Yellow or green mucus does not automatically indicate a bacterial infection requiring antibiotics. During a common cold, it’s normal for nasal discharge to thicken and change color from clear to yellow or green. This is typically due to the viral infection and can last up to 10 days.

Sinusitis in Children: When Antibiotics Might Be Necessary

Sinusitis refers to inflammation of the nasal and sinus linings. While viruses or allergies commonly cause sinusitis, bacteria can sometimes be the culprit. Bacterial sinusitis may require antibiotic treatment if your child exhibits the following symptoms:

• Cold symptoms lasting longer than 10 days without improvement
• Thick yellow or green mucus accompanied by a fever higher than 102°F (39°C) for at least 3 or 4 days
• Facial pain with fever

In these less common scenarios, your pediatrician may consider prescribing antibiotics. However, it’s essential to consult with your child’s doctor for a proper diagnosis and treatment plan.

Ear Infections: Do They Always Require Antibiotics?

Contrary to popular belief, not all ear infections necessitate antibiotic treatment. In fact, at least half of all ear infections resolve without antibiotics. Many ear infections are caused by viruses and do not respond to antibiotic therapy. Even some bacterial ear infections will clear up on their own without medication.

When Might Antibiotics Be Prescribed for Ear Infections?

Your pediatrician may recommend antibiotics if your child has:

• A high fever
• Severe ear pain
• Infection in both eardrums

Managing Ear Pain Without Antibiotics

If your child’s doctor determines that antibiotics are not necessary, they will suggest comfort care measures to alleviate ear pain. These may include:

1. Over-the-counter pain relievers such as acetaminophen or ibuprofen (dosed appropriately for your child’s age and size)
2. Warm compresses applied to the affected ear
3. Elevation of the head during sleep

It’s important to note that over-the-counter cold medicines, including decongestants and antihistamines, are not recommended for young children and do not help clear up ear infections.

Sore Throats: When Are Antibiotics Appropriate?

Not all sore throats require antibiotic treatment. Most sore throats, especially those accompanied by runny nose and cough, are caused by viruses. In these cases, antibiotics are ineffective and unnecessary.

Strep Throat: A Bacterial Infection Requiring Antibiotics

Strep throat, caused by group A streptococci bacteria, is one instance where antibiotics are typically prescribed. However, it’s important to note that children under 3 years old rarely get strep throat.

Diagnosing Strep Throat

If your child’s doctor suspects strep throat based on symptoms, a strep test should be performed. Antibiotics will usually be prescribed only if the test is positive. This approach ensures that antibiotics are used appropriately and only when necessary.

Potential Side Effects of Antibiotics in Children

While antibiotics can be life-saving when used correctly, they can also cause side effects. Understanding these potential adverse reactions is crucial for parents.

How Common Are Antibiotic Side Effects in Children?

Side effects occur in up to 1 in 5 children who take antibiotics. The frequency and severity of these side effects can vary depending on the specific antibiotic and the child’s individual response.

Common Side Effects of Antibiotics

Some of the most frequently observed side effects include:

• Rashes
• Allergic reactions
• Nausea
• Diarrhea
• Stomach pain

It’s crucial to inform your child’s doctor if your child has had any previous reactions to antibiotics. This information helps guide future treatment decisions and prevents potentially serious allergic reactions.

Antibiotic Resistance: A Growing Concern in Pediatric Care

Antibiotic resistance is a significant global health issue that affects children as well as adults. When bacteria develop resistance to antibiotics, it becomes more challenging to treat infections effectively.

How Does Antibiotic Resistance Develop?

Antibiotic resistance occurs when bacteria evolve to survive the effects of antibiotics. This can happen through various mechanisms, including:

• Genetic mutations that allow bacteria to neutralize or expel antibiotics
• Acquiring resistance genes from other bacteria
• Forming protective biofilms that antibiotics cannot penetrate

Consequences of Antibiotic Resistance in Pediatric Care

The development of antibiotic-resistant bacteria can lead to:

1. Longer-lasting illnesses
2. More complicated treatment regimens
3. Higher medical costs
4. Increased risk of spreading resistant bacteria to others

To combat antibiotic resistance, it’s crucial to use these medications judiciously and only when absolutely necessary.

Promoting Responsible Antibiotic Use in Children

As parents and caregivers, we play a vital role in ensuring the appropriate use of antibiotics for our children. Here are some guidelines to follow:

Partnering with Your Pediatrician

Maintaining open communication with your child’s doctor is crucial. Don’t hesitate to ask questions about prescribed treatments, including:

• Why is an antibiotic being prescribed?
• What are the potential side effects?
• Are there alternative treatments available?
• How long should the antibiotic be taken?

Following Prescription Instructions Carefully

If your child is prescribed antibiotics, it’s essential to:

1. Complete the entire course of antibiotics, even if your child starts feeling better
2. Administer the medication at the prescribed intervals
3. Never share antibiotics between children or save them for future use

Supporting Your Child’s Immune System

Promoting overall health can help your child’s body fight off infections naturally. Consider these strategies:

• Ensure your child gets adequate sleep
• Promote a balanced diet rich in fruits and vegetables
• Encourage regular physical activity
• Teach and reinforce good hygiene practices, such as handwashing

Alternative Approaches to Managing Childhood Illnesses

When antibiotics are not necessary, there are several ways to help your child feel better and manage symptoms effectively.

Supportive Care for Viral Infections

For viral infections like colds and flu, focus on providing comfort and supporting your child’s immune system:

• Ensure plenty of rest and hydration
• Use saline nasal drops or sprays to relieve congestion
• Run a cool-mist humidifier to moisten the air
• Offer warm liquids to soothe sore throats

Over-the-Counter Medications

While not always necessary, certain over-the-counter medications can help alleviate symptoms:

1. Acetaminophen or ibuprofen for fever and pain relief
2. Honey (for children over 1 year old) to soothe coughs
3. Throat lozenges for older children to ease sore throats

Always consult with your pediatrician before giving any medication to your child, especially for children under 6 years old.

The Future of Antibiotic Use in Pediatric Care

As our understanding of infectious diseases and the human microbiome continues to evolve, so too does our approach to treating childhood illnesses.

Advancements in Diagnostic Tools

Researchers are developing more rapid and accurate diagnostic tests to differentiate between viral and bacterial infections. These advancements may lead to more targeted use of antibiotics in the future.

Exploring Alternative Therapies

Scientists are investigating novel approaches to treating bacterial infections, including:

• Bacteriophage therapy: Using viruses that specifically target harmful bacteria
• Probiotics: Harnessing beneficial bacteria to combat pathogens
• Immune system modulators: Enhancing the body’s natural defense mechanisms

While these approaches are still in various stages of research and development, they hold promise for reducing our reliance on traditional antibiotics.

Personalized Medicine in Pediatric Infectious Diseases

The field of personalized medicine is also making strides in pediatric care. By analyzing a child’s genetic makeup and microbiome, doctors may soon be able to tailor treatments more effectively, potentially reducing the need for broad-spectrum antibiotics.

As we continue to navigate the complex landscape of childhood illnesses and antibiotic use, it’s crucial for parents, healthcare providers, and researchers to work together. By promoting responsible antibiotic use, exploring alternative treatments, and staying informed about the latest developments in pediatric care, we can ensure the best possible health outcomes for our children while preserving the effectiveness of these vital medications for future generations.

Antibiotics for Children: 10 Common Questions Answered

Using antibiotics when they are not the right medicine will not help. In fact, it may even cause more harm than good. Why? Because antibiotics only treat infections caused by bacteria—not viruses. Plus, like all medications, antibiotics have side effects.

Before prescribing an antibiotic, your pediatrician will find out if it is the right medicine to treat your child’s infection.

1. My child has a really bad cold. Why won’t the doctor prescribe an antibiotic?

Colds are almost always caused by viruses. Antibiotics only treat bacteria. In general, most
common cold symptoms—such as runny nose, cough, and congestion—will get better without using any medicines.

Many young children—especially those in
child care—can get 6 to 8 colds per year.

2. Don’t some colds turn into bacterial infections? So why wait to start an antibiotic?

In most cases, bacterial infections do not follow viral infections. Treating viral infections with antibiotics almost never prevents bacterial infections; however, they may instead cause diarrhea or other side effects.

3. Isn’t a nose draining yellow or green mucus a sign of a bacterial infection?

Yellow or green mucus in the nose does not automatically mean that antibiotics are needed. During a common cold, it is normal for mucus from the nose to get thick and to change from clear to yellow or green. This is most often from viral infection, which can last for up to 10 days.

Sinusitis is a term that means inflammation of the lining of the nose and sinuses. A virus or allergy can cause sinusitis and, in some cases, bacteria can be the cause.

Your child may have bacterial sinusitis if they have these signs:

• cold symptoms that last longer than 10 days and are not improving
• thick yellow or green mucus with a
  fever higher than 102°F (39°C) for at least 3 or 4 days
• facial pain with fever

In these uncommon situations, an antibiotic may be needed. See The Difference Between Sinusitis and a Cold.

4. Aren’t antibiotics supposed to treat ear infections?

At least half of all ear infections go away without antibiotics. Many true ear infections are caused by viruses and do not require antibiotics. Even some of the ear infections that are caused by bacteria will go away on their own without antibiotics. If your pediatrician believes your child’s ear infection does not need antibiotics, they will talk with you about comfort care. They can recommend the best ways to help relieve your child’s ear pain until the infection runs its course.

Because pain is often the first and most uncomfortable symptom of ear infection, your child’s doctor will suggest pain medicine to ease your child’s pain.
Acetaminophen and
ibuprofen are over-the-counter pain medicines that may help lessen the pain. Be sure to use the right dose for your child’s age and size. In most cases, pain and fever will improve within the first 1 to 2 days.

Over-the-counter cold medicines (decongestants and

antihistamines) don’t help clear up ear infections and are not recommended for young children. Ear drops may help ear pain for a short time, but always ask your child’s doctor if your child should use these drops.

Your child’s doctor may prescribe antibiotics if your child has a higher fever, more severe ear pain or infection in both eardrums. See Ear Infection Information, Middle Ear Infections, and Your Child and Ear Infections.

5. Aren’t antibiotics used to treat all sore throats?

No. Most sore throats are caused by viruses. If your child has sore throat, runny nose and a cough, a virus is the likely cause. In these cases, a test for “strep” should not be given.

Antibiotics should only be used to treat sore throats caused by
group A streptococci. Infection caused by this type of bacteria is called “strep throat.”

Children under 3 years old rarely get strep throat.

If your child’s doctor suspects strep throat based on your child’s symptoms, a strep test should always be performed. If the test is positive, antibiotics will be usually be prescribed. See The Difference between a Sore Throat, Strep & Tonsillitis and When a Sore Throat is a More Serious Infection.

6. Do antibiotics cause side effects?

Side effects occur in up to 1 in 5 children who take an antibiotic. Side effects may include rashes,
allergic reactions, nausea, diarrhea, and
stomach pain. Make sure you let your child’s doctor know if your child has had a reaction to antibiotics in the past.

Sometimes a rash will occur during the time a child is taking an antibiotic. However, not all rashes are considered allergic reactions. Tell your child’s doctor if you see a rash that looks like hives (red welts) soon after taking the first dose of an antibiotic; this may be an allergic reaction.

7. How long does it take an antibiotic to work?

Most bacterial infections improve within 48 to 72 hours of starting an antibiotic. If your child’s symptoms get worse or do not improve within 72 hours, call your child’s doctor.

8. Can antibiotics lead to resistant bacteria?

The repeated use and misuse of antibiotics can lead to resistant bacteria. Resistant bacteria are bacteria that are no longer killed by the antibiotics commonly used to treat them. These resistant bacteria can also be spread to other children and adults.

It is important that your child use the antibiotic that is most specific for your child’s infection, rather than an antibiotic that would treat a broader range of infections.

If your child develops an antibiotic-resistant infection, a special type of antibiotic may be needed. Sometimes, these medicines need to be given by IV (vein) in the hospital.

9. What are antiviral medicines?

An antiviral medicine may be prescribed for children that are at higher risk of becoming severely ill if they get the flu. For most other viruses causing cough and cold symptoms, there are no antiviral medicines that work.

10. How can I use antibiotics safely?

• 
  Give the medicine exactly as directed.
  See Medication Safety Tips and Using Liquid Medicines.

• 
  Don’t use one child’s antibiotic for a sibling or friend; you may give the wrong medicine and cause harm.

• 
  Keep antibiotics and other prescription medicine in a secure place. Count and monitor the number of pills you have and lock them up. Ask your friends, family members, and babysitters to do the same.

• 
  Dispose leftover antibiotics and other prescription medication. Return leftover prescriptions to a hospital, doctor’s office, or pharmacy. Many counties now offer “take-back” events to collect unused medication. For more information, see Promote Safe Storage and Disposal of Opioids and All Medications.

More information

• 
  Antibiotics for a Sore Throat, Cough or Runny Nose?

• 
  Coughs and Colds: Medicines or Home Remedies

• 
  When to Keep Your Child Home from Child Care

• Causes of Earaches: KidsDoc Symptom Checker

• COVID-19 and Other Respiratory Illnesses: How Are They Different?

Last Updated

11/1/2022

Source

American Academy of Pediatrics Section on Infectious Diseases (Copyright © 2022)

The information contained on this Web site should not be used as a substitute for the medical care and advice of your pediatrician. There may be variations in treatment that your pediatrician may recommend based on individual facts and circumstances.

The History of Antibiotics – HealthyChildren.org

Antibiotics: What’s in a Name?

The term antibiotics literally means “against life”; in this case, against microbes. There are many types of antibiotics—antibacterials, antivirals, antifungals, and antiparasitics. Some drugs are effective against many organisms; these are called broad-spectrum antibiotics. Others are effective against just a few organisms and are called narrowspectrum antibiotics. The most commonly used antibiotics are antibacterials. Your child may have received ampicillin for an ear infection or penicillin for a strep throat.

When a child is sick, parents worry. Even if he has only a mild cold that makes him cranky and restless or an achy ear that only hurts a little, these times can be very stressful. Of course, you want him to get the best possible treatment. For many parents, this means taking him to the pediatrician and leaving the office with a prescription for antibiotics.

But that isn’t necessarily what will happen during the doctor’s visit. After examining your youngster, your pediatrician may tell you that based on your child’s symptoms and perhaps some test results, antibiotics just are not necessary.

Many parents are surprised by this decision. After all, antibiotics are powerful medicines that have eased human pain and suffering for decades. They have even saved lives. But most doctors aren’t as quick to reach for their prescription pads as they once were. In recent years, they’re realizing there is a downside to choosing antibiotics—if these medicines are used when they’re not needed or they’re taken incorrectly, they can actually place your child at a greater health risk. That’s right—antibiotics have to be prescribed and used with care, or their potential benefits will decrease for everyone.

A Look Back

Serious diseases that once killed thousands of youngsters each year have been almost eliminated in many parts of the world because of the widespread use of childhood vaccinations.

In much the same way, the discovery of antimicrobial drugs (antibiotics) was one of the most significant medical achievements of the 20th century. There are several types of antimicrobials—antibacterials, antivirals, antifungals, and antiparasitic drugs. (Although antibacterials are often referred to by the general term antibiotics, we will use the more precise term.) Of course, antimicrobials aren’t magic bullets that can heal every disease. When used at the right time, they can cure many serious and life-threatening illnesses.

Antibacterials are specifically designed to treat bacterial infections. Billions of microscopic bacteria normally live on the skin, in the gut, and in our mouths and throats. Most are harmless to humans, but some are pathogenic (disease producing) and can cause infections in the ears, throat, skin, and other parts of the body. In the pre-antibiotic era of the early 1900s, people had no medicines against these common germs and as a result, human suffering was enormous. Even though the body’s disease-fighting immune system can often successfully fight off bacterial infections, sometimes the germs (microbes) are too strong and your child can get sick. For example,

• Before antibiotics, 90% of children with bacterial meningitis died. Among those children who lived, most had severe and lasting disabilities, from deafness to mental retardation.

• Strep throat was at times a fatal disease, and ear infections sometimes spread from the ear to the brain, causing severe problems.

• Other serious infections, from tuberculosis to pneumonia to whooping cough, were caused by aggressive bacteria that reproduced with extraordinary speed and led to serious illness and sometimes death.

The Emergence of Penicillin

With the discovery of penicillin and the dawning of the antibiotic era, the body’s own defenses gained a powerful ally. In the 1920s, British scientist Alexander Fleming was working in his laboratory at St. Mary’s Hospital in London when almost by accident, he discovered a naturally growing substance that could attack certain bacteria. In one of his experiments in 1928, Fleming observed colonies of the common Staphylococcus aureus bacteria that had been worn down or killed by mold growing on the same plate or petri dish. He determined that the mold made a substance that could dissolve the bacteria. He called this substance penicillin, named after the Penicillium mold that made it. Fleming and others conducted a series of experiments over the next 2 decades using penicillin removed from mold cultures that showed its ability to destroy infectious bacteria.

Before long, other researchers in Europe and the United States started recreating Fleming’s experiments. They were able to make enough penicillin to begin testing it in animals and then humans. Starting in 1941, they found that even low levels of penicillin cured very serious infections and saved many lives. For his discoveries, Alexander Fleming won the Nobel Prize in Physiology and Medicine.

Drug companies were very interested in this discovery and started making penicillin for commercial purposes. It was used widely for treating soldiers during World War II, curing battlefield wound infections and pneumonia. By the mid- to late 1940s, it became widely accessible for the general public. Newspaper headlines hailed it as a miracle drug (even though no medicine has ever really fit that description).

With the success of penicillin, the race to produce other antibiotics began. Today, pediatricians and other doctors can choose from dozens of antibiotics now on the market, and they’re being prescribed in very high numbers. At least 150 million antibiotic prescriptions are written in the United States each year, many of them for children.

Problems With Antibiotics

The success of antibiotics has been impressive. At the same time, however, excitement about them has been tempered by a phenomenon called antibiotic resistance. This is a problem that surfaced not long after the introduction of penicillin and now threatens the usefulness of these important medicines.

Almost from the beginning, doctors noted that in some cases, penicillin was not useful against certain strains of Staphylococcus aureus (bacteria that causes skin infections). Since then, this problem of resistance has grown worse, involving other bacteria and antibiotics. This is a public health concern. Increasingly, some serious infections have become more difficult to treat, forcing doctors to prescribe a second or even third antibiotic when the first treatment does not work.

In light of this growing antibiotic resistance, many doctors have become much more careful in the way they prescribe these medicines. They see the importance of giving antibiotics only when they’re absolutely necessary. In fact, one recent survey of office-based physicians, published in JAMA: The Journal of the American Medical Association in 2002, showed that doctors lowered the number of antibiotic prescriptions they prescribed for children with common respiratory infections by about 40% during the 1990s.

Antibiotics should be used wisely and only as directed by your pediatrician. Following these guidelines, their life-saving properties will be preserved for your child and generations to come.

The information contained on this Web site should not be used as a substitute for the medical care and advice of your pediatrician. There may be variations in treatment that your pediatrician may recommend based on individual facts and circumstances.

Fundamentally new antibiotics have been created – expert material, Lahta Clinic

A new group of antibiotics with a unique mechanism of attacking bacteria has been discovered, which makes these drugs very promising, primarily in the context of overcoming the global crisis of drug resistance in bacterial pathogens.

Newly developed corbomycin and complestatin have a previously unknown bacterial killing effect, which is achieved by blocking the functions of the cell wall of the pathogen. The discovery was made while studying a family of antibiotics called glycopeptides, which are substances produced by certain soil bacteria.

The research team has demonstrated in a mouse model that novel antibacterial drugs can stop infections caused by drug-resistant strains of Staphylococcus aureus, a pathogen known to cause many serious illnesses.

The results of the study were published on February 12, 2020 in “ Nature “.

Lead Author, PhD in Biochemistry and Biomedical Sciences, McMaster University (Hamilton, Canada) Beth Culp explains:

“Every bacterium is surrounded by a cell wall that gives it shape and is a source of strength. Antibiotics, like penicillin, prevent the normal development of the membrane, but the drugs we discovered act in the exact opposite way – they do not allow the membrane to collapse, which critically blocks cell division. It’s like a bacterium being imprisoned in its own membrane – it won’t be able to multiply or grow. ”

Studying the genetics of already known microbes that produce glycopeptides, scientists first of all paid attention to those genes to which resistance effects were not observed, bearing in mind the prospect of using such substances as alternative antibiotics.

“Our hypothesis was that if genetically different microorganisms produce substances with an antibacterial effect, then the mechanism of this action should be different,” says B. Culp .

That the target and target is the cell wall was confirmed by the team using imaging technology in collaboration with the Yves Brun team at the University of Montreal.

In closing Beth Culp says:

“This approach could be extended to the development of other antibacterial drugs. Since our research discovered one completely new antibiotic, we have discovered several more substances in this group with a similar mechanism of action that was not known before. ”

Team leader is Professor Jerry Wright at the Antibiotic Development Center. David Braley at the Michael J. DeGroot Institute for Infectious Diseases at McMaster University. The project was funded by the Canadian Institutes of Medical Research and the Ontario Research Foundation.

Science Daily

Russian scientists have found a new family of antibiotics from the group of lipoglycopeptides

In an era of rapidly spreading antibiotic resistance, scientists are trying hard to find new antibiotics to expand the arsenal of anti-infective drugs. A large team of Russian researchers recently reported the discovery of a new family of lipoglycopeptide antibiotics synthesized by bacterial strain Streptomyces . The properties of two substances from this group, gausemycins A and B, have been studied in detail. The extremely unusual chemical structure allows us to hope for an atypical mechanism of action of these antibiotics.

No matter how hard scientists are now trying to create new antibiotics: they are looking for them in a variety of natural sources, chemically modifying already known substances, developing inhibitors of systems that provide protection against antibiotics, and even creating completely synthetic antibiotics using machine learning. The first path most often ends in failure, because antimicrobial substances isolated from natural substrates, as a rule, turn out to be either already known antibiotics or their modifications. But there is an exception to every rule.

You can get acquainted with other materials of “Biomolecules” dedicated to antibiotics in the thematic collection “ Antibiotics “.

Broth obtained by fermentation by the bacterium Streptomyces sp. INA-Ac-5812, in fact, is a whole cocktail of peptide antibiotics, as already reported in previous studies [1]. In general, antibiotics of a peptide nature have long been included in clinical practice. Currently, peptide antibiotics with significantly different mechanisms of action are known. Peptide antibiotic 9Doctors have been using 0053 vancomycin for years, and of course the bacteria have found a way to evade it. But now its semi-synthetic analogues are being sold ( oritavancin , telavancin , cefilavancin ), which are used in clinical practice with varying degrees of success. Some antibiotics that are cyclic peptides, such as colistin and daptomycin , are used as antibiotics of last choice for especially dangerous infections when all other antibiotics are ineffective and the patient is life or death.

The authors of the article under discussion have managed from a mixture of antibiotics produced by Streptomyces sp. INA-Ac-5812, purify previously unknown lipoglycopeptide antibiotics, which were named gausemycins A and B [2]. Initially, they were described as fluorescent substances with a wide spectrum of antibacterial activity. As it turned out later, the fluorescent properties of gausemycins are due to the presence of chlorinated amino acid 4-chloro-L-kynurenine [3]. Previously, this amino acid was found only in representatives of one family of antibiotics, taromycins [4].

In general, the structure of gausemycins turned out to be surprisingly unusual. They are macrocyclic peptides of 14 amino acids, including non-proteinogenic and D-amino acids (in particular, they include D-leucine in the seventh position).

Some of the structural motifs found in hausemycins are extremely rare for substances of natural origin. For example, tyrosine glycosylated with pentose has not yet been found in natural peptides. Moreover, in gausemycins, tyrosine is glycosylated not by anything, but by pentose, known as arabinose, which is almost never found in natural glycopeptides. Thus, glycosylation of tyrosine by arabinose can be considered a unique feature of gausemycins among all substances of natural origin.

In addition, β-hydroxyglutamic acid , which is rarely found in natural substances, as well as 3-amino-4-hydroxyphenylbutyric acid and N ^ε – (β-alaninoyl) ornithine , which before that, also not found in natural compounds. Gauzemycins A and B differ from each other by the radical attached to the second ornithine residue. In gausemycin A, the amino group of ornithine remains free, while in gausemycin B it is acylated with β-alanine (Fig. 1).

Figure 1. Structural formulas and structure diagram of hausemycins A and B

[2], figure adapted

How is such a complex molecule synthesized? The authors of the work found a large biosynthetic gene cluster, consisting of 68 open reading frames, which provides the synthesis of gausemycins. Among these reading frames there is a nonribosomal peptide synthetase containing 14 modules responsible for incorporating fragments with a specific amino acid sequence into molecules. Of interest was the origin of rare amino acids in the gausemycins. It is known that 4-chloro-L-kynurenine is synthesized from tryptophan [5], and the study of the biosynthesis of gausemycins made it possible to prove that previously unknown 3-amino-4-hydroxyphenylbutyric acid is synthesized from phenylalanine. An elegant method was used to prove it: the producer strain was fed with fluorinated phenylalanine and the incorporation of a fluorine atom into this unique amino acid was observed.

How can gausemycins help in the fight against antibiotic resistance? Due to their extremely unusual structure, they have a number of properties that distinguish them from other lipopeptide antibiotics. Gauzemycins do not have a classical calcium ion binding site, which is different from anionic lipopeptides, including the recently described malacidins and cadazids.

Researchers have shown that gausemycins have strong activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), one of the most dangerous strains of multidrug-resistant bacteria. But against enterococci and Koch’s bacilli ( Mycobacterium tuberculosis ) gausemycins were powerless.

How do gausemycins work? It turned out that they cause cell lysis, and only some cells showed membrane damage, and most of them had nothing left at all. In addition, gausemycins do not affect the synthesis of the cell wall and do not cause the accumulation of its precursors.

To test that gausemycins do induce gradual membrane permeabilization, Bacillus subtilis 9 cells 0054 was exposed to gausemycins and stained with SYTOX, which stains DNA green and does not penetrate whole membranes, and with FM 4-64, which stains membranes. Experience confirmed that gausemycins damage membranes and cause cell death after an hour. So, according to the mechanism of action, gausemycins are close to the antibiotic daptomycin, which, like gausemycins, slowly kills cells, in contrast to the antibiotic nisin, which causes a very rapid death of bacteria (Fig. 2).

Figure 2. Gauzemycins and daptomycin cause cell death by forming pores in them. You can see how the green dye gradually penetrates the cells and stains their DNA. The antibiotic nisin was used as a control, which immediately causes the formation of pores in cell membranes and leads to the complete death of the bacterial culture.

[2], modified figure

Why do gausemycins have such a narrow spectrum of action? Long-term studies of the mechanism of action of daptomycin have shown that daptomycin in the presence of calcium ions forms a complex with the lipid phosphatidylglycerol and some cell wall precursors, resulting in delocalization of the cell wall biosynthesis apparatus. Daptomycin is also quite effective against enterococci, whose membranes contain a lot of phosphatidylglycerol, and gausemycins, as we remember, do not act on enterococci. So what is the mechanism of action of gausemycins? Why is the spectrum of bacteria they act on so narrow? Further research on these unusual antibiotics is needed to answer these questions.

We spoke with Vera Alferova , an employee of the G.F. Gause and one of the first authors of the study, about some aspects of the action of gausemycins and their possible prospects in clinical practice.

E.M.: Why don’t gausemycins affect Gram-negative bacteria? After all, they can, theoretically, violate the integrity of the outer membrane, which is unlikely to benefit bacteria.

VA: The mechanism of action of gausemycin is not limited to pore formation. According to current data, it, like daptomycin, implements a complex mechanism of action that requires the fulfillment of a number of conditions. It is too early to speak more specifically about the target, but for daptomycin the lipid composition of the membrane plays a key role, it is very likely that the specificity for hausemycin is due to the same principle. At the same time, the outer membrane of gram-negative bacteria is very different from the membranes of gram-positive bacteria, including the lipid composition. The spectrum of activity of gausemycin is narrow even among gram-positive bacteria, apparently, it can neither damage the outer membrane of gram-negative bacteria, nor overcome it.

E. M.: What are the prospects for the use of gausemycins in clinical practice?

VA: It is unlikely that gausemycin alone will be used in clinical practice, as it is similar to the already well-tested daptomycin. At the moment, we see that its spectrum of activity is narrower than that of the antibiotic used. It may be of interest only as a domestic analogue of a well-known drug, but its implementation requires enormous financial costs. Gauzemycin is of interest primarily from a scientific point of view, since understanding the mechanism of its action will also shed light on daptomycin, and will also allow, using chemical modification, to obtain semi-synthetic derivatives with an optimized structure and properties that are more in demand in modern clinical practice.

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