Early-life acquisition of antimicrobial resistance in newborn children from low- and middle-income countries (2022)

Early-life acquisition of antimicrobial resistance in newborn children from low- and middle-income countries (1)

Every year, almost 7 million potentially serious bacterial infections are estimated to occur in newborns, resulting in more than 550,000 annual neonatal deaths. Most of these infections and deaths happen in LMICs, where often scarce resources can limit the capacity to diagnose and treat sepsis. These problems are further complicated by the global rise of antimicrobial resistance (AMR), particularly the rapid spread of gram-negative bacteria that are resistant to antibiotics—including Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae that are no longer susceptible to ß-lactam antibiotics, such as ampicillin and ceftazidime. AMR is already estimated to account for approximately 5 million deaths a year worldwide, and has been predicted to result in 10 million annual deaths by 2050.

Despite neonatal sepsis representing such a major health problem in LMICs, it is still unclear how, when, and where newborn babies acquire life-threatening infections. Furthermore, the factors associated with the presence of AMR in these cases are also still being elucidated. For example, there have been no studies in LMICs examining whether the presence of antibiotic-resistant bacteria in mothers is linked to the development of sepsis in their newborns.

In a new study published in Nature Microbiology, Dr. Maria Carvalho, Dr. Kirsty Sands and a network of international colleagues decided to look at the presence of antibiotic resistance genes (ARGs) in the gut microbiota—the collection of microbes that are present in the human gut—of mothers and their babies from 7 LMICs in Africa and South Asia. As part of the "Burden of Antibiotic Resistance in Neonates from Developing Societies" study, or BARNARDS—a network of 12 clinical sites across Bangladesh, Ethiopia, India, Nigeria, Pakistan, Rwanda and South Africa—they recruited 35,040 mothers and 36,285 neonates. From these, they collected 18,148 rectal swabs (15,217 from mothers and 2,931 from neonates, including 626 with sepsis), which were used to grow the bacteria present in these samples and assess the presence of clinically important ARGs in the microbiota of mothers and their babies. The authors found that a large number of samples carried genes linked to antibiotic resistance, suggesting that AMR is far more widespread in these settings than previously anticipated. For example, samples from around 1 in 5 neonates (18.5%) were positive for blaNDM, a gene that encodes New Delhi metallo-beta-lactamase, which is an enzyme that can destroy ß-lactam antibiotics including the commonly used carbapenems, resulting in the bacteria being resistant against this drug. Importantly, the researchers found that ARGs were present in neonates within hours of birth, indicating that initial colonization of the newborns with antibiotic-resistant bacteria occurred at birth or soon after, likely through contact with the mother or from the hospital environment.

(Video) Early life acquisition of AMR in newborn children from low and middle income countries

The samples collected from mothers and neonates were also used to identify the bacteria resistant to antibiotics. In total, the authors isolated 1,072 gram-negative bacteria, with the majority of these being K. pneumoniae, E. coli and E. cloacae. Whole genome sequencing revealed that while these bacteria are quite diverse across different locations, there are clear clusters associated with specific countries and hospitals. The BARNARDS team identified some cases in which bacterial isolates were shared by different neonates attending the same clinical site, suggesting that in some cases transmission of resistant bacteria from the hospital environment or between newborns may have occurred. Furthermore, the genomic analyses showed that some E. coli isolates were indistinguishable between mothers and newborns, supporting that mother-to-child transmission may occur during or after labor.

Finally, the researchers identified risk factors associated with the carriage of ARGs, looking at features associated with water, sanitation, and hygiene (WASH) and prior infections. The team found that frequent handwashing by mothers reduced the risk of carrying resistance genes (compared to occasional handwashing), whereas this risk was increased if mothers had reported an infection or taken antibiotics in the 3 months prior to being enrolled in the study. The carriage of such ARGs by mothers was also associated with an increased risk of adverse birth outcomes and neonatal sepsis.

These findings demonstrate the high prevalence of antibiotic resistance in the microbiota of mothers and their neonates in LMICs, including within hours after birth. Furthermore, the study highlights that better understanding the routes of ARG transmission, including mother-to-child and within the clinical environment, is essential to prevent neonatal sepsis. Finally, the results reinforce the importance of access to safe water, sanitation, and good hygiene to reduce AMR and lower neonatal sepsis and mortality rates in LMICs.

Professor Tim Walsh, who supervised the study, stressed the novelty of the findings: "This article demonstrates two novel observations. The first is that the incidence of AMR carriage, including carbapenem resistance, is extremely worrying, not only in South Asia but also in some parts of Africa. The second is that the incidence of carbapenem resistance is really high in newborn babies, demonstrating that AMR carriage occurs within a few days of life. Clearly, this research poses many questions about transmission and also about how the acquisition of these drug-resistant strains might impact on the growth of the baby—questions we are currently working to address within the IOI and with our collaborators."

Dr. Kirsty Sands, who co-led the study, highlighted how the study starts to elucidate the factors governing the spread of AMR: "The BARNARDS group worked together for over seven years to produce one of the largest studies that analyzes gut bacteria of women and their neonates. This study shows that transmission dynamics can be very complex, as we found links between carriage, infection, and sanitation and hygiene. We need to continue our research to fully understand these transmission dynamics, which could help to guide better infection prevention and control measures."

As explained by Dr. Maria Carvalho, who co-led the research, the study also promoted capacity building in local sites: "BARNARDS developed and implemented a standardized methodology to attain the common objective of minimizing the impact of morbidity and mortality in neonates from African and South Asian countries. We also looked at the specific needs for each site. For example, BARNARDS set up an additional maternity ward (20 beds) and a Microbiology Lab in the Murtala Muhammad Specialist Hospital Kano, Nigeria. Capacity building throughout the network at different levels (clinical, research and outreach) was a big achievement of BARNARDS."

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Dr. Rabaab Zahra, who led the study in Islamabad, Pakistan, stressed the importance of these findings for understanding and controlling the spread of AMR: "Based on our knowledge of AMR prevalence, we had speculated certain levels of resistance in neonates but didn't think this started so early on in life. This raises concerns about our policies on antibiotics use, along with hygiene and infection control practices in healthcare facilities."

The impact of the study in informing current practices in some of the hospitals was also highlighted by Dr. Fatima Modibbo, who co-led the study in Kano, Nigeria: "Prior to the start of the research at the hospital in Kano, blood cultures were not routinely implemented. However, during the study we were able to identify bacterial resistance patterns in blood cultures of neonates presenting with sepsis that led to life saving changes in empirical drug treatments and a reduction in the neonatal mortality rates."

The full paper, "Antibiotic resistance genes in the gut microbiota of mothers and linked neonates with or without sepsis from low and middle-income countries," is published in Nature.

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More information:Maria Carvalho, Antibiotic resistance genes in the gut microbiota of mothers and linked neonates with or without sepsis from low- and middle-income countries, Nature Microbiology (2022). DOI: 10.1038/s41564-022-01184-y. www.nature.com/articles/s41564-022-01184-y

Journal information:Nature

, Nature Microbiology

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Citation: Early-life acquisition of antimicrobial resistance in newborn children from low- and middle-income countries (2022, August 4) retrieved 3 September 2022 from https://phys.org/news/2022-08-early-life-acquisition-antimicrobial-resistance-newborn.html

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.

FAQs

What are the causes of antimicrobial resistance? ›

Misuse and overuse of antimicrobials are the main drivers in the development of drug-resistant pathogens. Lack of clean water and sanitation and inadequate infection prevention and control promotes the spread of microbes, some of which can be resistant to antimicrobial treatment.

Why is antimicrobial resistance a growing problem? ›

Antibiotic resistance occurs naturally, but misuse of antibiotics in humans and animals is accelerating the process. A growing number of infections – such as pneumonia, tuberculosis, gonorrhoea, and salmonellosis – are becoming harder to treat as the antibiotics used to treat them become less effective.

What are the five general mechanisms of resistance? ›

The mechanisms of resistance can be broken down into the following:
  • Enzyme inactivation and modification.
  • Modification of the antibiotics target site.
  • Overproduction of the target.
  • Replacement of the target site.
  • Efflux and reduced permeability.

What do we highlight when we talk about antimicrobial resistance? ›

Antimicrobial resistance occurs when microorganisms such as bacteria, viruses, fungi and parasites change in ways that render the medications used to cure the infections they cause ineffective. When the microorganisms become resistant to most antimicrobials they are often referred to as “superbugs”.

What is the most common type of antimicrobial resistance? ›

MRSA is one of the most common antibiotic-resistant bacteria. Symptoms of MRSA infection often begin as small red bumps on the skin that can progress to deep, painful abscesses or boils, which are pus-filled masses under the skin.

What are the mechanisms of antimicrobial resistance? ›

The three fundamental mechanisms of antimicrobial resistance are (1) enzymatic degradation of antibacterial drugs, (2) alteration of bacterial proteins that are antimicrobial targets, and (3) changes in membrane permeability to antibiotics.

What are the 4 types of antibiotic resistance? ›

Antimicrobial resistance mechanisms fall into four main categories: (1) limiting uptake of a drug; (2) modifying a drug target; (3) inactivating a drug; (4) active drug efflux.

What 3 factors play a prominent role in the increase of antimicrobial resistance? ›

What causes AMR?
  • AMR happens naturally.
  • AMR increases when we use antibiotics.
  • Poor hygiene and infection prevention and control.
  • People travelling.
  • Related links.
31 Oct 2017

Who is at risk for antibiotic resistance? ›

Who is at risk of antibiotic-resistant infections? Everyone is at risk of antibiotic-resistant infections, but those at the greatest risk for antibiotic-resistant infections are young children, cancer patients, and people over the age of 60.

What are the 3 different categories of antimicrobial agents? ›

There are three types of public health antimicrobials: sterilizers, disinfectants, and sanitizers.

What are the four basic methods by which antimicrobial agents work? ›

Basis of Antimicrobial Action

Various antimicrobial agents act by interfering with (1) cell wall synthesis, (2) plasma membrane integrity, (3) nucleic acid synthesis, (4) ribosomal function, and (5) folate synthesis.

How do you test for antimicrobial resistance? ›

The most commonly used technique for identifying antimicrobial susceptibility is determination of MIC. This method has the purpose of quantifying the minimum concentration of antimicrobial that inhibits the apparent growth of bacteria when carried out in agar or broth.

What is the difference between antibiotic and antimicrobial resistance? ›

Distinguishing between antibiotic and antimicrobial resistance is important. Antibiotic resistance refers to bacteria resisting antibiotics. Antimicrobial resistance (AMR) describes the opposition of any microbe to the drugs that scientists created to kill them.

What are examples of antimicrobials? ›

What are examples of antimicrobials?
  • Penicillin (an antibiotic).
  • Valacyclovir (an antiviral agent).
  • Fluconazole (an antifungal medication).
  • Praziquantel (an antiparasite medication).
27 Apr 2021

What is antimicrobial resistance simple definition? ›

Antimicrobial resistance happens when germs like bacteria and fungi develop the ability to defeat the drugs designed to kill them. That means the germs are not killed and continue to grow.

What are the most common antibiotic-resistant diseases? ›

Leading antimicrobial drug-resistant diseases
  • Mycobacterium tuberculosis. The bacterium that causes tuberculosis (TB) ...
  • C. difficile. ...
  • VRE. (Vancomycin-resistant Enterococci) ...
  • MRSA. (Methicillin-resistant Staphylococcus aureus) ...
  • Neisseria gonorrhoea. The bacterium that causes gonorrhea. ...
  • CRE.
25 Jan 2018

Which of the following are the three factors that should be know before selecting an antimicrobial drug? ›

The WG agreed on the following basic criteria for the selection of antimicrobial agents: 1) the agent should be useful when screening various resistant bacteria, 2) the agent should serve as a useful guide for physicians and residents when selecting antimicrobial agents, and 3) the agent should be useful for ...

What are the classification of antimicrobial agents? ›

Antimicrobial agents are classified into several categories, i.e. inhibitors for bacterial cell wall such as beta-lactam drugs, fosfomycin, and vancomycin; inhibitors for protein biosynthesis such as tetracyclibnes, macrolides, aminoglycoside antibiotics; inhibitors for DNA synthesis such as 4-quinolones; inhibitors ...

What are the 5 major targets of antimicrobial agents? ›

Five bacterial targets have been exploited in the development of antimicrobial drugs: cell wall synthesis, protein synthesis, ribonucleic acid synthesis, deoxyribonucleic acid (DNA) synthesis, and intermediary metabolism.

What are the two ways that bacteria can acquire antibiotic resistance? ›

There are two main ways that bacterial cells can acquire antibiotic resistance. One is through mutations that occur in the DNA of the cell during replication. The other way that bacteria acquire resistance is through horizontal gene transfer.

What is antimicrobial resistance PDF? ›

Antimicrobial resistance (AMR) occurs when bacteria, parasites, viruses and fungi become resistant to antimicrobial drugs that are used for treating the infections they cause.

What are two causes of multidrug resistant organisms? ›

Multidrug-resistant organisms develop when antibiotics are taken longer than necessary or when they are not needed. At first, only a few bacteria may survive treatment with an antibiotic. The more often the antibiotics are used, the more likely it is that resistant bacteria will develop.

What 3 factors play a prominent role in AMR? ›

What causes AMR?
  • AMR happens naturally.
  • AMR increases when we use antibiotics.
  • Poor hygiene and infection prevention and control.
  • People travelling.
  • Related links.
31 Oct 2017

What are some examples of antibiotic resistance? ›

Important examples are:
  • methicillin-resistant Staphylococcus aureus (MRSA)
  • vancomycin-resistant Enterococcus (VRE)
  • multi-drug-resistant Mycobacterium tuberculosis (MDR-TB)
  • carbapenem-resistant Enterobacteriaceae (CRE) gut bacteria.

What is meant by antimicrobial resistance? ›

Antimicrobial resistance happens when germs like bacteria and fungi develop the ability to defeat the drugs designed to kill them. That means the germs are not killed and continue to grow.

What are the 4 most common multidrug-resistant organisms? ›

These include methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci species (VRE), carbapenemase-producing Enterobacteriaceae, and Gram-negative bacteria that produce extended spectrum beta-lactamases (ESBLs).

What are the three most common multidrug-resistant organisms? ›

Common multidrug-resistant organisms are usually bacteria: Vancomycin-Resistant Enterococci (VRE) Methicillin-resistant Staphylococcus aureus (MRSA) Extended-spectrum β-lactamase (ESBLs) producing Gram-negative bacteria.

How can we prevent antibiotic resistance? ›

Taking antibiotics only when they are needed is an important way you can protect yourself and your family from antibiotic resistance. Talk to your doctor about the best treatment if you are sick. Never pressure your doctor to prescribe an antibiotic.

What is the best method for preventing health care associated infections? ›

Proper use of personal protective equipment (e.g., gloves, masks, gowns), aseptic technique, hand hygiene, and environmental infection control measures are primary methods to protect the patient from transmission of microorganisms from another patient and from the health care worker.

What are the classification of antimicrobial agents? ›

Antimicrobial agents are classified into several categories, i.e. inhibitors for bacterial cell wall such as beta-lactam drugs, fosfomycin, and vancomycin; inhibitors for protein biosynthesis such as tetracyclibnes, macrolides, aminoglycoside antibiotics; inhibitors for DNA synthesis such as 4-quinolones; inhibitors ...

What are the two types of antibiotic resistance? ›

There are two important types of genetic mechanisms that can give rise to antibiotic resistance: mutation and acquisition of new genetic material.

Who is most at risk for antibiotic resistance? ›

Who is at risk of antibiotic-resistant infections? Everyone is at risk of antibiotic-resistant infections, but those at the greatest risk for antibiotic-resistant infections are young children, cancer patients, and people over the age of 60.

What are the most common antibiotic-resistant diseases? ›

Leading antimicrobial drug-resistant diseases
  • Mycobacterium tuberculosis. The bacterium that causes tuberculosis (TB) ...
  • C. difficile. ...
  • VRE. (Vancomycin-resistant Enterococci) ...
  • MRSA. (Methicillin-resistant Staphylococcus aureus) ...
  • Neisseria gonorrhoea. The bacterium that causes gonorrhea. ...
  • CRE.
25 Jan 2018

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