Category: Antibiotics

Categories : Antibiotics Diseases, Syndromes and ConditionsTags : 1 Comment

AMR Caused Over 1.2 Million Deaths Globally in 2019

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Methicillin-resistant Staphylococcus aureus (MRSA) bacteria. Credit: CDC

Globally, infections by antimicrobial-resistant (AMR) bacteria caused more than 1.2 million deaths worldwide in 2019, according to a study published in The Lancet. It is the largest and most comprehensive one to date of this critical issue.

Lower-income countries are worst affected but antimicrobial resistance remains a global threat, the researchers wrote.

The researchers emphasised that investment in new drugs is urgently needed, as well as vaccination and better antimicrobial stewardship.

The estimate of global deaths from AMR, is based on the researchers’ analysis of 204 countries, assuming the counterfactual that the bacteria responsible would be antibiotic-susceptible.

Of the 4.95 million deaths in which AMR played a role, 1.27 million were directly attributable to it. In 2019, 860 000 deaths were estimated from HIV and 640 000 from malaria.

Most of the AMR-related deaths resulted from lower respiratory infections, such as pneumonia, and bloodstream infections, which can lead to sepsis.

Deaths from AMR were estimated to be highest in sub-Saharan Africa at 23.7 deaths per 100 000, and lowest in North Africa and the Middle East at 11.2 per 100 000. Young children are at most risk, with about one in five deaths linked to AMR being among the under-fives.

The researchers also noted that “resistance is high for multiple classes of essential agents, including beta-lactams and fluoroquinolones.”

MRSA (methicillin-resistant Staphylococcus aureus) was particularly deadly, while E. coli, K. pneumoniae, S. pneumoniae, A. baumannii, and P. aeruginosa were associated with high levels of resistance. The researchers wrote that “each of these leading pathogens is a major global health threat that warrants more attention, funding, capacity building, research and development, and pathogen-specific priority setting from the broader global health community.”

They also recommend that immunity to these pathogens be built up by vaccination, and since currently only S. pneumoniae has a vaccine readily available, these will need to be developed and deployed as a matter of urgency. They noted several limitations to their study, the first being the sparsity of data drawn from low- and middle-income countries, which may in fact lead to an underestimate of the prevalence of AMR. Secondly, there is the possibility of multiple sources of bias inherent in combining datasets from different providers. Finally, there may be bias in surveillance, eg if cultures are drawn only if a patient is unresponsive to antibiotics, leading to an overestimate.

Source: The Lancet

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Breathing New Life into Old Antibiotics

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Source: Pixabay CC0

Scientists may have hit upon a way to make frontline antibiotics once again effective against the deadly bacteria that cause pneumonia.

The international team originally developed this as a potential treatment for disorders such as Alzheimer’s, Parkinson’s and Huntington’s diseases to break bacterial resistance to commonly used frontline antibiotics.

Led by University of Melbourne Professor Christopher McDevitt, this discovery may see the comeback of readily available and cheap antibiotics, such as penicillin and ampicillin, as effective weapons in the fight against the rapidly rising threat of antibiotic resistance.

In a paper published in Cell Reports, Prof McDevitt and colleagues described how they discovered a way to break bacterial drug resistance and then developed a therapeutic approach to rescue the use of the antibiotic ampicillin to treat drug-resistant bacterial pneumonia caused by Streptococcus pneumoniae in a mouse model of infection.

The World Health Organization (WHO) last year named antibiotic resistance as one of the greatest threats to global health, food security, and development. Rising numbers of bacterial infections such as pneumonia, tuberculosis, gonorrhoea, and salmonellosis are becoming harder to treat as the antibiotics lose effectiveness against them.

Prof McDevitt’s prior work on bacterial antibiotic resistance using zinc ionophores led to collaborations with University of Queensland’s Professor Mark Walker and Griffith University’s Professor Mark von Itzstein from the Institute for Glycomics.

“We knew that some ionophores, such as PBT2, had been through clinical trials and shown to be safe for use in humans,” Prof von Itzstein said.

Prof Walker said that “as a group, we realised that if we could repurpose these safe molecules to break bacterial resistance and restore antibiotic efficacy, this would be a pathway to a therapeutic treatment. What we had to do was show whether PBT2 broke bacterial resistance to antibiotic treatment without leading to even greater drug resistance.”

“We focused on bacterial pneumonia and the most commonly used antibiotics. We thought that if we could rescue frontline antibiotics and restore their use for treating common infections, this would solve a global problem,” Prof McDevitt added.

An important component was the research from Prof McDevitt’s group that led to making the treatment effective.

“We knew from earlier research that the immune system uses zinc as an innate antimicrobial to fight off infection. So, we developed our therapeutic approach with PBT2 to use the body’s antimicrobial zinc to break antibiotic resistance in the invading bacteria,” he said.

“This rendered the drug-resistant bacteria susceptible to the antibiotic ampicillin, restoring the effectiveness of the antibiotic treatment in the infected animals.”

Collecting the data required for a clinical trial of PBT2 in combination with antibiotics is the next step, said Prof McDevitt.

“We also want to find other antibiotic-PBT2 combinations that have therapeutic potential for treatment of other bacterial infections,” he said.

“Our work shows that this simple combination therapy is safe, but the combinations require testing in clinical trials. What we need now is to move forward with further testing and pharmacology.”

Source: University of Melbourne

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Hedgehog Discovery Shows MRSA Evolved Before the Advent of Antibiotics

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A surprising discovery in hedgehogs showed that a variant of the MRSA superbug appeared in nature well before antibiotics use in humans and livestock, which has traditionally been blamed for its emergence.

Staphylococcus aureus first developed resistance to the antibiotic methicillin around 200 years ago, according to a large international study which has traced the genetic history of the bacteria.

The finding comes from research showing that up to 60% of hedgehogs in Denmark and Sweden carry a type of MRSA called mecC-MRSA. The new study also found high levels of MRSA in swabs taken from hedgehogs across their range in Europe and New Zealand. Their findings were published in the journal Nature.

The researchers believe that antibiotic resistance evolved in S. aureus as an adaptation to having to exist on hedgehog skin next to the fungus Trichophyton erinacei, which produces its own antibiotics. The discovery of this centuries-old antibiotic resistance predates antibiotic use in medical and agricultural settings.

“Using sequencing technology we have traced the genes that give mecC-MRSA its antibiotic resistance all the way back to their first appearance, and found they were around in the nineteenth century,” said Dr Ewan Harrison, a senior author of the study.

He added: “Our study suggests that it wasn’t the use of penicillin that drove the initial emergence of MRSA, it was a natural biological process. We think MRSA evolved in a battle for survival on the skin of hedgehogs, and subsequently spread to livestock and humans through direct contact.”

Antibiotic resistance in human pathogens was previously thought to be a modern phenomenon, driven by the clinical use of antibiotics. Antibiotic misuse is now accelerating the process, with antibiotic resistance rising dangerously worldwide.

Since nearly all antibiotics used today arose in nature, the researchers say it is likely that resistance to them already exists in nature too. Overuse of any antibiotic in humans or livestock will favour resistant strains of the bacteria, causing it to lose effectiveness over time.

“This study is a stark warning that when we use antibiotics, we have to use them with care. There’s a very big wildlife ‘reservoir’ where antibiotic-resistant bacteria can survive – and from there it’s a short step for them to be picked up by livestock, and then to infect humans,” said Professor Mark Holmes, a senior author of the report.

In 2011, mecC -MRSA was identified in human and dairy cow populations, which was assumed to have arisen due to the large number of antibiotics cows are routinely given.

MRSA was first identified in patients in 1960, and around 1 in 200 of all MRSA infections are caused by mecC-MRSA. Due to its resistance to antibiotics, MRSA is much harder to treat than other bacterial infections. The World Health Organization now considers MRSA one of the world’s greatest threats to human health.

Human infections are rare with mecC-MRSA however, even though it has been present in hedgehogs for more than 200 years.

Source: University of Cambridge

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Signs of Antibiotic ‘Pre-resistance’ Identified for the First Time

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Drug-resistant, Mycobacterium tuberculosis bacteria, the pathogen responsible for causing the disease tuberculosis (TB). A 3D computer-generated image. Credit: CDC

In a first of its kind study, researchers have spotted signs of antibiotic ‘pre-resistance’ in bacteria for the first time, indicating that they have the potential to develop drug resistance in the future.

The findings, published in Nature Communications, will allow doctors in the future to select the best treatments for bacterial infections.

Mycobacterium tuberculosis (TB) was the second leading infectious cause of death after COVID in 2020, killing 1.5m people. It can be cured if treated with the right antibiotics, but treatment is lengthy and many people most at risk lack access to adequate healthcare. Drug-resistant TB can develop when people do not finish their full course of treatment, or when drugs are not available or are of poor quality.

Multi-drug resistant TB represents a huge, unsustainable burden and totally drug resistant strains have been detected in a handful of countries. As health systems struggle to cope with the pandemic, progress on TB treatment globally has slowed.

To better understand TB for developing new drugs, this study has identified for the first time how to pre-empt drug resistance mutations before they have occurred. Dubbed ‘pre-resistance’ when a pathogen has a greater inherent risk of developing resistance to drugs in the future.

By analysing thousands of bacterial genomes, the study has potential application to other infectious diseases and paves the way towards personalised pathogen ‘genomic therapy’ – which chooses drugs according to the pathogen, preventing drug resistance.

The culmination of 17 years’ work, the study built up a TB bacterial ‘family tree’  from 3135 different tuberculosis samples. Computational analysis identified the ancestral genetic code of bacteria that then went on to develop drug resistance. The team identified the key changes associated with the development of resistance by looking through the ‘branches’ of the family tree to see which had the most potential for developing drug resistance.

Variations in the TB genome predicted that a particular branch would likely become drug resistant, and then validated their findings in an independent global TB data set.

Dr Grandjean, senior author of the study, said: “We’re running out of options in antibiotics and the options we have are often toxic – we have to get smarter at using what we have to prevent drug resistance.

“This is the first example of showing that we can get ahead of drug resistance. That will allow us in the future to use the pathogen genome to select the best treatments.”

Source: EurekAlert!

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New Antibacterial Molecules Identified

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Researchers have identified a new group of molecules with an antibacterial effect against many antibiotic-resistant bacteria. Since the properties of the molecules can easily be altered chemically, the hope is to develop new, effective antibiotics with few side effects. The study appears in PNAS.

Increasing antibiotic resistance is a great concern as few new antibiotics have been developed in the past 50 years.

Most antibiotics work by inhibiting the bacteria’s ability to form a protective cell wall, causing the bacteria to crack (cell lysis). Besides the well-known penicillin, which inhibits enzymes building up the wall, newer antibiotics such as daptomycin or the recently discovered teixobactin bind to a special molecule, lipid II. All bacteria need lipid II as a building block for the cell wall. Antibiotics that bind to Lipid II are usually very large and complex molecules and therefore more difficult to improve with chemical methods. These molecules are in addition mostly inactive against a group of problematic bacteria, which are surrounded by an additional layer, the outer membrane, that hinders penetration of these antibacterials.

“Lipid II is a very attractive target for new antibiotics. We have identified the first small antibacterial compounds that work by binding to this lipid molecule, and in our study, we found no resistant bacterial mutants, which is very promising,” says Birgitta Henriques Normark, professor at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, and one of the article’s three corresponding authors.

For this study, published in PNAS, researchers tested a large number of chemical compounds for their ability to lyse pneumococci – the most common cause of community-acquired pneumonia. After a careful follow-up of active compounds from this screening, the researchers found that a group of molecules called THCz inhibits the formation of the cell wall of the bacterium by binding to lipid II. The molecules could also prevent the formation of the sugar capsule that pneumococci need to escape the immune system and to cause disease.

Small molecules offer several benefits, noted Fredrik Almqvist, professor at Umeå University and one of the corresponding authors: “The advantage of small molecules like these is that they are more easy to change chemically. We hope to be able to change THCz so that the antibacterial effect increases and any negative effects on human cells decrease.”

Laboratory work with THCz showed it has an antibacterial effect against many antibiotic-resistant bacteria, such as methicillin-resistant staphylococci (MRSA), vancomycin-resistant enterococci (VRE), and penicillin-resistant pneumococci (PNSP). An antibacterial effect was also found against gonococci, which causes gonorrhoea, and mycobacteria, bacteria that can cause severe diseases such as tuberculosis in humans. None of the bacteria managed to develop resistance to THCz in a laboratory environment.

“We will now also initiate attempts to change the THCz molecule, allowing it to penetrate the outer cell membrane found in some, especially intractable, multi-resistant bacteria,” says Tanja Schneider, professor at the Institute of Pharmaceutical Microbiology at the University of Bonn and one of the corresponding authors.

Source: Karolinska Institutet

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Insects Carry a Range of Antimicrobial-resistant Bacteria

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A study published in Nature Microbiology has for the first time provided compelling evidence of connections between antimicrobial-resistant bacteria causing surgical-site infections and insects and other arthropods. Among these bacteria are those with resistance to drug-of-last-resort. 

Antimicrobial resistance (AMR) could render many of the current mainstay and last-resort antibiotics useless, resulting in many more deaths from previously treatable infections. A UN report estimated in 2019 that AMR could lead to ten million deaths per year, and cost the world $100 trillion, by 2050.

“Similar to our experience over the last eighteen months with the pandemic, a problem currently seen from afar will quickly come into focus much closer to home” said Professor Tim Walsh at Oxford University

The report found that:

  • About 20% of the flies, cockroaches, spiders, moths, and ants were carrying carbapenem resistance.
  • Of these, 70-80% were carrying extended spectrum cephalosporin resistance, that is, enzymes that confer resistance to most beta-lactam antibiotics, including penicillins, cephalosporins, and the monobactam aztreonam.
  • Currently there are about 18 million flies to every human, but conservative global warming projections estimate insect and fly population will double if temperatures increase by 1.5 degrees.
  • By 2080 there could be around 50 000 trillion flies carrying carbapenem resistance and spreading AMR across the planet.

“Similar to our experience over the last eighteen months with the pandemic, a problem currently seen from afar will quickly come into focus much closer to home,” said Prof Walsh. “The clinical burden of AMR is most felt in low-middle income countries, but the increase in global temperatures, due to climate change, will result in a significant increase in flies and many other insects and a subsequent increase in the global velocity of antibiotic resistance.” Prof. Tim Walsh, Oxford University.

AMR is a pervasive issue, stretching from hospitals to farming and human waste processing. Resistance can spread within hospitals, communities, farms, and wastewater systems, and domestic animals can share AMR microorganisms with humans.

One tactic is to repurpose previously developed drugs that did not work for humans and use these for animals, buying time for us to develop new drugs.

Another is to rethink hospital prevention and infection control measures, especially in lower- and middle-income countries. Further research into how arthropods disseminate AMR and improving healthcare infrastructure to reduce the spread of AMR by arthropods.

“Most antibiotics currently used on animals are also the same that are used in humans, creating a pool where bacteria can evolve to evade drugs and then reinfect humans,” said Prof Tim Walsh of Oxford University.

“There is no silver bullet when it comes to tackling the worldwide threat of AMR,” he added. “The Ineos Oxford Institute for AMR Research is committed to finding non-human antibiotic therapies and feeds for animals, addressing the increase in AMR in human infections and raising awareness of this hidden threat to human health. But this is a global medical crisis that ultimately will only be resolved with a global response.”

Source: Oxford University

Categories : Antibiotics PaediatricsTags :

Amoxicillin Flops in Simple Paediatric Chest Infections

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Photo by Andrea Piacquadio from Pexels

The largest randomised placebo-controlled trial of the antibiotic amoxicillin for treating paediatric chest infections has found it is little more effective at relieving symptoms than placebo. 

While viruses are believed to cause many chest infections in children, whether antibiotics are effective in treating chest infections in children is still debated. In adults, research has shown that antibiotics are not effective for uncomplicated chest infections.

In the study, published in The Lancet, researchers sought to test whether amoxicillin reduces the duration of moderately bad symptoms in children presenting with uncomplicated (non-pneumonic) lower respiratory tract chest infections in primary care. The trial recruited 432 children aged six months to 12 years-old with acute uncomplicated chest infections from primary care practices, randomised to receive either amoxicillin or a placebo three times a day for seven days. Doctors or nurse-prescribers assessed symptoms at the start of the study and parents, with help from their children where possible, completed a daily symptom diary.

Only a small, non-significant, difference in symptom duration was seen between the two groups: children given the placebo had symptoms which were rated moderately bad or worse for around 6 days on average after seeing the doctor, and those given antibiotics only recovered 13% faster.

This held true even for groups where chest sounds were present, there was a fever, was rated more unwell by a doctor, coughing up phlegm or had a rattly chest, or the child was short of breath.

Just four children in the placebo group and five in the antibiotic group required further assessment at hospital. Parental costs such as leave taken or over-the-counter remedies, were very similar in both groups.

The study lead author, Professor Paul Little, said: “”Children given amoxycillin for chest infections where the doctor does not think the child has pneumonia do not recover much more quickly.

“Indeed, using amoxicillin to treat chest infections in children not suspected of having pneumonia is not likely to help and could be harmful. Overuse of antibiotics, which is dominated by prescribing of antibiotics in primary care, particularly when they are ineffective, can lead to side effects and the development of antibiotic resistance.”

Study co-author Alastair Hay, a GP and University of Bristol professor, added: “The ARTIC PC trial is one of the very few studies to report on the effectiveness of prescribing antibiotics among younger children presenting with chest infections in primary care. It was designed to be able to detect a clinically important 3-day improvement in symptom duration.

“Our results suggest that unless pneumonia is suspected, clinicians should provide ‘safety-netting’ advice such as explaining what illness course to expect and when it would be necessary to re-attend but not prescribe antibiotics for most children presenting with chest infections.”

Source: University of Bristol

Categories : Antibiotics Obstetrics & GynaecologyTags :

Azithromycin Protects Pregnancies in Countries with Malaria

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A review has found that the common antibiotic azithromycin taken during pregnancy reduces low birth weight and premature births in countries where malaria is endemic.

The systematic review of 14 studies in African and Asia, published in The Lancet EClinicalMedicine, found that azithromycin, reduced low birth weight and prematurity but didn’t lower infant deaths, infections and hospital admissions.

Azithromycin, an inexpensive antibiotic widely used to treat chest and ear infections, has been specifically used in the past in pregnancy to treat STIs and, alongside other antimalarial drugs, to prevent adverse consequences of malaria on maternal and foetal outcomes and caesarean wound infections.

Murdoch Children’s Research Institute (MCRI) researcher Dr Maeve Hume-Nixon said it was not clear whether azithromycin would improve perinatal and neonatal outcomes in non-malaria endemic settings, and the potential harm on stillbirth rates needed further investigation.

Dr Hume-Nixon said these findings emphasised the importance of similar MCRI-led research currently being done in Fiji.

“This review found that there was uncertainty about the potential benefits of this intervention on neonatal deaths, admissions and infections, and potential harmful effects on stillbirth despite biological reasons why this intervention may have benefits for these outcomes,” she said.

“Therefore, results from studies like ours underway in Fiji will help to better understand the effect of this intervention on these outcomes.”

The Bulabula MaPei study is a randomised controlled clinical trial testing if azithromycin given to women in labour, prevents maternal and infant infections.

Globally, infections account for 21% of 2.4 million neonatal deaths per year and 52% of all under-five deaths, disproportionately occurring in low- and middle-income countries.

About five million cases of pregnancy-related infections occur in mothers each year as well, resulting in 75 000 maternal deaths.

MCRI Professor Fiona Russell said the large clinical trials in Africa and Asia, along with the MCRI-led trial in Fiji, were likely to inform global policy related to maternal child health and hopefully benefit infants and mothers around the world.

“Administration of azithromycin during labour may be a cheap and simple intervention that could be used to improve neonatal death rates in low and middle-income countries, alongside strengthening of maternal child health services,” she said. “This study, together with other large clinical trials, will add to evidence for the consideration of new international maternal and child health guidelines.”

Source: Murdoch Childrens Research Institute

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Human Breast Milk Could Yield Antibiotic Secrets

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Researchers believe that antibacterial properties of sugars in human breast milk could be harnessed for new antimicrobial therapies.

Group B Streptococcus (GBS) bacteria are a common cause of blood infections, meningitis and stillbirth in newborns, and are becoming resistant to antibiotics. Researchers have now discovered that human milk oligosaccharides (HMOs), short strings of sugar molecules abundant in breast milk, can help prevent GBS infections in human cells and tissues and in mice. This might yield new antibiotic treatments, the researchers believe. 

“Our lab has previously shown that mixtures of HMOs isolated from the milk of several different donor mothers have antimicrobial and antibiofilm activity against GBS,” says Rebecca Moore, who is presenting the work at a meeting of the American Chemical Society (ACS). “We wanted to jump from these in vitro studies to see whether HMOs could prevent infections in cells and tissues from a pregnant woman, and in pregnant mice.” Moore is a graduate student in the labs of Steven Townsend, PhD, at Vanderbilt University and Jennifer Gaddy, PhD, at Vanderbilt University Medical Center.

According to the US Centers for Disease Control and Prevention, about 2000 babies in the U.S. get GBS each year, with 4-6% of them dying from it. The bacteria are often transferred from mother to baby during labour and delivery. An expectant mother who tests positive for GBS is usually given intravenous antibiotics during labor to help prevent early-onset infections, which occur during the first week of life. Notably, late-onset infections (which happen from one week to three months after birth) are more common in formula-fed than breastfed infants, suggesting breast milk has factors which could help protect against GBS. If so, the sugars could be a replacement for current antibiotics which are steadily becoming less effective.

The researchers studied the effects of combined HMOs from several mothers on GBS infection of placental macrophages and of the gestational membrane. “We found that HMOs were able to completely inhibit bacterial growth in both the macrophages and the membranes, so we very quickly turned to looking at a mouse model,” Moore says. They examined whether HMOs could prevent a GBS infection from spreading through the reproductive tract of pregnant mice. “In five different parts of the reproductive tract, we saw significantly decreased GBS infection with HMO treatment,” Moore notes.

To determine which HMOs and other oligosaccharides have these antimicrobial effects and why, the researchers made an artificial two-species microbiome with GBS and the beneficial Streptococcus salivarius species growing in a tissue culture plate, separated by a semi-permeable membrane. Then, the researchers added oligosaccharides that are commonly added to infant formula, called galacto-oligosaccharides (GOS), which are derived from plants. In the absence of the sugar, GBS suppressed the growth of the “good” bacteria, but GOS helped this beneficial species grow. “We concluded that GBS is producing lactic acid that inhibits growth, and then when we add the oligosaccharide, the beneficial species can use it as a food source to overcome this suppression,” Moore explained.
The first HMOs tested did not have this effect, but Townsend says it’s likely that one or more of the over 200 unique sugars in human milk will show activity in the artificial microbiome assay. There are likely two reasons why HMOs can treat and prevent GBS infection: they prevent pathogens from sticking to tissue surfaces and forming a biofilm, and they could also act as a prebiotic by promoting good bacteria growth.

“HMOs have been around as long as humans have, and bacteria have not figured them out. Presumably, that’s because there are so many in milk, and they’re constantly changing during a baby’s development,” Townsend said. “But if we could learn more about how they work, it’s possible that we could treat different types of infections with mixtures of HMOs, and maybe one day this could be a substitute for antibiotics in adults, as well as babies.”

Source: American Chemical Society

Categories : Antibiotics COVIDTags :

Bacterial Superinfections in COVID Rarer Than Expected

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Only 21 percent of patients with severe pneumonia caused by SARS-CoV-2 have a documented bacterial superinfection at the time of intubation, resulting in potential overuse of antibiotics, according to new research.

Superinfection occurs when another, usually different, infection is superimposed on the initial infection. In this case, it is bacterial pneumonia during severe viral pneumonia.

Dr Wunderink and co-authors reported their findings in a study published online in the Journal of Respiratory and Critical Care Medicine, which shows that the usual clinical criteria used to diagnose bacterial pneumonia could not distinguish between those with bacterial superinfection and those with severe SARS-CoV-2 infection only.

According to the authors, there is weak evidence behind current guidelines recommending that patients with SARS-CoV-2 pneumonia receive empirical antibiotics on hospital admission for suspected bacterial superinfection. In other published clinical trials of patients with SARS-CoV-2 pneumonia, rates of superinfection pneumonia are unexpectedly low.
“More accurate assessment other than just reviewing clinical parameters is needed to enable clinicians to avoid using antibiotics in the majority of these patients, but appropriately use antibiotics in the 20-25 percent who have a bacterial infection as well,” said Dr Wunderink.

The team conducted an observational study to determine the prevalence and cause of bacterial superinfection at the time of initial intubation and the incidence and cause of subsequent bacterial ventilator-associated pneumonia (VAP) in 179 patients with severe SARS-CoV-2 pneumonia which required mechanical ventilation.

The researchers analysed 386 bronchoscopic bronchoalveolar lavage fluid samples from patients, and actual antibiotic use was compared with guideline-recommended therapy. Bacterial superinfection within 48 hours of intubation was detected in 21 percent of patients; 72 patients (44.4 percent) developed at least one VAP episode; and 15 (20.8 percent) of initial VAPs were caused by difficult-to-treat bacteria.

The authors found that in patients with severe SARS-CoV-2 pneumonia, bacterial superinfection at the time of intubation occurred in less than 25 percent of patients. Guideline-based empirical antibiotic management at the time of intubation would have resulted in antibiotic overuse.

The researchers believe that their findings have multiple implications for antibiotic guidelines: “Rapid diagnostic tests are important for helping identify suspected pneumonia in intubated patients. This can have major clinical implications because the current approach of using clinically defined risk factors for suspected methicillin-resistant staphylococcus aureus (MRSA) or pseudomonas bacteria as the cause of pneumonia still grossly overestimate the true incidence of these pathogens. In addition, the recommendation for empirical antibiotic treatment of worsening viral community-acquired pneumonia (now requiring intubation) may need to be revisited. This is not only true for SARS-CoV-2 but potentially for severe influenza as well.”

“An accurate diagnosis of suspected pneumonia allows clinicians to safely avoid or use narrow spectrum antibiotics for many patients,” Dr Wunderink added.  “While multiple interventions impact mortality in these critically ill patients, the low mortality in our study with more limited antibiotic treatment suggests that our approach was safe.”

Source: American Thoracic Society