Decade-long #warming accelerates #antibiotic #resistance in #grassland soils

 

Abstract

Soils are critical reservoirs of antibiotic-resistance genes (ARGs), which are strongly shaped by microbial interactions and environmental conditions and are therefore highly sensitive to disturbance. Although climate warming is recognized as one of the most significant disturbances to microbial communities and their functions, its impacts on soil resistomes remain poorly understood. Here we investigated the effects of decade-long experimental warming on ARGs in grassland soils using integrated experimental and computational approaches. Our results revealed that ARG abundance substantially increased (23.9%) under warming—particularly glycopeptide- and rifamycin-resistance genes. Warming specifically enriched Actinomycetota hosts, including various potential plant pathogens, and enhanced ARG mobility. Large-scale unprecedented isolates-based phenotypic analyses also validated that warming increased bacterial resistance to multiple antibiotics. Further mechanistic analyses revealed that warming increased ARG abundance primarily through co-selection of resistance genes physically linked to adaptive traits (for example, thermal tolerance and nitrogen assimilation) and positive selection for thermal tolerance genes, which could be further amplified via horizontal gene transfer. Together, these findings convincingly demonstrate that climate warming substantially accelerates soil antibiotic resistance at genomic, ecological and evolutionary levels, with broad implications for public health and environmental sustainability in a warming world.

Source: 

Link: https://www.nature.com/articles/s41586-026-10413-x

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#Survival #trends in patients with difficult-to-treat, #antibiotic-resistant, Gram-negative #infections in the era of next-generation antibiotics in the #USA: a retrospective cohort study

 

Summary

Background

Difficult-to-treat resistant (DTR) Gram-negative infections show resistance to all first-line antibiotics (ie, β-lactams and fluoroquinolones) and have a 40% greater mortality rate than susceptible infections. New antibiotics are now available with improved safety and efficacy and with in-vitro activity against DTR infections; however, their influence on the outcomes of patients with DTR infections remains unclear. We aimed to evaluate whether and why mortality in patients with DTR infections has changed since the introduction of these newer antibiotics in the USA.

Methods

In this retrospective cohort study in the USA, adult patients (aged ≥18 years) with a DTR Gram-negative infection, defined as microbiological evidence of DTR Enterobacterales, Pseudomonas aeruginosa, or Acinetobacter baumannii and receipt of at least 3 consecutive days of any antibiotic therapy, were identified from hospitals reporting microbiology data in the PINC-AI Healthcare Database. We characterised the proportion of inpatient encounters receiving newer DTR-active antibiotics, traditional DTR-active antibiotics, and non-DTR-active antibiotics. We used a generalised linear mixed model with marginal predictions to examine changes in in-hospital mortality, defined as death or discharge to hospice, over the study period when adjusting for patient-related and treatment-related factors (including receipt of a new antibiotic and receipt of in-vitro discordant initial therapy), hospital-related factors (including the availability of newer antibiotics and corresponding susceptibility testing), and COVID-19 pandemic-related factors. A three-way interaction term for time (year), pathogen, and infection site (ie, bloodstream and non-bloodstream) was included given the expected differences in mortality.

Findings

Between Jan 1, 2016, and Aug 31, 2023, 8 319 398 adult inpatient encounters with available microbiology data were recorded from 471 hospitals, of which 9384 (0.11%) encounters had microbiological evidence of an eligible DTR organism. 5065 (54·0%) of these 9384 encounters, from 262 hospitals, met the inclusion criteria for DTR Gram-negative infections and were included in the study. Among this cohort, the prescription of newer antibiotics, as well as the availability of newer antibiotics and their corresponding susceptibility tests, increased substantially from 2016 to 2023. Although the proportion of encounters in which the patient received a newer antibiotic as initial therapy increased from 4% (21 of 589) in 2016 to 15% (34 of 234) in 2023, in most cases (196 [84%] of 234) patients continued to receive in-vitro discordant initial antibiotic therapy, even in 2023. We observed no change in the average marginal effect (the average percentage change per year) for adjusted mortality between 2016 and 2023 for Enterobacterales (0.1% [95% CI −1.1 to 1.4]), P aeruginosa (−0.7% [−1.7 to 0.3]), or A baumannii (−0.4% [−1.8 to 0.9]) infections. When dichotomised into bloodstream and non-bloodstream infections, the marginal effect for adjusted mortality remained unchanged over time for most pathogen and site combinations, with the exception of P aeruginosa bloodstream infections, for which a decrease was observed (−4.5% [−8.2 to −0.60]).

Interpretation

Despite the availability of newer antibiotic agents, the estimated mortality and ongoing use of in-vitro discordant initial antibiotics remains unacceptably high among patients with DTR infections in US hospitals. Prompt recognition of both the pathogen and resistance phenotype could be a crucial component in reducing mortality. Although notable, the decrease over time in adjusted mortality for P aeruginosa bloodstream infections should be considered hypothesis-generating because the cohort of patients with such infections was small.

Funding

US National Institutes of Health (NIH) Clinical Center; US National Cancer Institute; the Intramural Research Program of the US National Heart, Lung, and Blood Institute; the US National Institute of Allergy and Infectious Diseases; and the US Food and Drug Administration.

Research in context

Evidence before this study

Difficult-to-treat resistance is a resistance phenotype describing Gram-negative pathogens that show resistance to all first-line, safe and effective traditional antibiotic options (ie, β-lactams [including carbapenems] and fluoroquinolones). As a result, difficult-to-treat resistant (DTR) infections are associated with high mortality, of which they are a better predictor than susceptible infections. Several new antibiotics have been introduced into the US market since 2014 and could provide more treatment options to patients with antimicrobial-resistant (AMR) infections such as DTR infections, for whom no safe and effective treatment exists. Evidence supporting a reduction in mortality after treatment with these new antibiotics, specifically in patients with AMR infections, is scarce. Understanding the population-level change in mortality following the implementation of these new antibiotic therapies could inform current priorities in therapeutic and diagnostic development to improve outcomes in this high-risk patient population. We searched PubMed from database inception to Dec 16, 2025, for studies with the Medical Subject Headings Major Topics “Bacterial Infections/mortality” AND “Drug Resistance, bacterial”, with no language restrictions. This search returned 426 publications. 34 articles evaluated trends in bacterial resistance over time and associated mortality among drug-resistant bacterial infections, of which 13 examined only Gram-positive bacterial infections and eight examined a period before the introduction of any of the newer antibiotics (ie, before 2014). Mortality estimates over time in the remaining 13 publications considered only discrete phenotypes for which alternative effective treatment options might exist, did not characterise the use of newer antibiotics within the study population, and did not adjust for relevant COVID-19 pandemic-related factors that are likely to affect the interpretation of mortality trends since 2020.

Added value of this study

This study leverages an administrative and clinical database to identify, to our knowledge, the largest cohort to date of hospitalised patients with DTR Gram-negative infections in the USA. We evaluate adjusted mortality trends in patients with DTR infections after the real-world introduction of six new antibiotics (ceftolozane–tazobactam, ceftazidime–avibactam, meropenem–vaborbactam, imipenem–relebactam, eravacycline, and cefiderocol) with broad spectra of activity and variable side-effect profiles. Trends in mortality were examined using a generalised linear mixed model adjusted for relevant patient-related, hospital-related, and COVID-19 pandemic-related covariates. The estimated probability of mortality across DTR Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii infections did not change from 2016 to 2023. When dichotomised into bloodstream and non-bloodstream infections, we identified a 4.5% annual reduction in the adjusted mortality for P aeruginosa bloodstream infections, albeit the sample size for this population was small (n=87). The trends in adjusted mortality for all other pathogen and infection-site combinations remained unchanged. These findings occurred in the setting of persistent and frequent use of in-vitro discordant initial empirical therapy despite a substantial increase in access to and use of newer antibiotic options.

Implications of all the available evidence

Our results underscore the importance of better understanding why survival has not improved across all DTR Gram-negative infections despite the availability of newer, safe, and effective broad-spectrum antibiotic options. The development and real-world implementation of improved rapid diagnostic platforms for early detection of resistant phenotypes could improve patient outcomes. Comparative trials of new antibiotics with increased representation of patients with highly resistant bacterial infections, namely DTR infections, could elucidate the true clinical benefit of newer antibiotics in their respective target populations. Exploration of additional non-antibiotic, host-directed therapies could address the immune dysregulation that might contribute to poor patient outcomes, even among those who die with susceptible infections.

Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(26)00020-4/fulltext?rss=yes

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#UK, #England: Expansion of #Meningitis B #vaccination offer to #Kent #Students (UKHSA, March 19 '26)

 

The Meningitis B vaccine will now be offered to everyone who has been offered preventative antibiotic treatment as part of this outbreak.

-- Vaccination will now be extended to everyone who has been offered preventative antibiotic treatment as part of this outbreak.

-- Preventative antibiotics – and vaccination – will also now be offered to the 6th form students (years 12 and 13) in schools and colleges in Kent where confirmed or probable cases are identified.

-- On a case-by-case basis, future risk assessment may also support use in other year groups or settings.

-- Students can, and should, continue to attend schools and colleges as normal. 

-- The NHS Kent and Medway website will be updated shortly with vaccination sites for those eligible.

-- The key intervention to protect people and halt the spread remains for people to come forward for antibiotic treatment. A single course of antibiotics is highly effective in preventing the contraction and spread of this disease in 90% of cases.

-- As a further precautionary measure, we are extending the offer of antibiotic prophylaxis and vaccine to any individuals who attended Club Chemistry from the 5 March until it closed voluntarily on 15 March.

-- 20,000 vaccines from the NHS supply will be made available to the private market, to ease current demand experienced by pharmacies. These will enter the private market within around 48 hours.

In response to the ongoing Meningitis B (MenB) outbreak in Kent, the UK Health Security Agency (UKHSA) is expanding the offer of preventative antibiotic treatment and vaccination to control the outbreak. 

Preventative antibiotic treatment and vaccination will now be offered to 6th sixth form students (years 12 and 13) in schools and colleges in Kent with confirmed or probable cases On a case-by-case basis, following risk assessment by the local health protection team, antibiotics and vaccination may also be made available to additional year groups. Students can, and should, continue to attend schools and colleges as normal.

In addition to the approximately 5,000 students who were initially contacted, vaccination will now be extended to everyone who has been offered preventative antibiotic treatment as part of this outbreak. This includes University of Kent students who live on the Canterbury Campus and other relevant halls of residence; close contacts of confirmed or suspected cases, and students in four education settings in Kent where cases have been confirmed. Anyone who visited Club Chemistry in Canterbury between 5 and 15 March will also be offered a vaccine and antibiotics as a precaution after one suspected case revisited the nightclub before it shut voluntarily.

This extension ensures that those most likely to have been in close contact with confirmed or suspected cases are offered longer term protection as early as possible.

The NHS Kent and Medway website will be updated shortly with vaccination sites for those eligible.

Patients eligible for antibiotics will now be able to request a vaccination and antibiotics from their local GP immediately – wherever they are in England.

While preventative antibiotics remain the key intervention to protect people and halt the spread of infection, vaccination is being offered as an additional measure to provide longer term protection for those at increased risk.

Given current demand on the private MenB vaccine market, 20,000 doses will also be released from NHS supply to support continuity of private provision, enabling up to 2,000 pharmacies to receive vaccines in the next 48 hours.

Professor Susan Hopkins, Chief Executive of the UK Health Security Agency, said: 

''By extending the vaccination programme to everyone who has been offered preventative antibiotics, we are taking an important additional step to protect those most likely to have been exposed. The message is simple: if you have had the antibiotic, you are also eligible for the vaccination.

People are reminded to remain alert to the signs and symptoms of invasive meningococcal disease and to seek urgent medical attention if they or someone they know becomes unwell.

Background 

Meningococcal disease (meningitis and sepsis) is an uncommon but serious disease caused by meningococcal bacteria. Very occasionally, the meningococcal bacteria can cause serious illness, (inflammation of the lining of the brain) and sepsis (blood poisoning), which can rapidly lead to sepsis. 

The onset of illness is often sudden and early diagnosis and treatment with antibiotics are vital. 

Early symptoms, which may not always be present, include: 

- a rash that doesn’t fade when pressed with a glass

- sudden onset of high fever

- severe and worsening headache

- stiff neck

- vomiting and diarrhoea

- joint and muscle pain

- dislike of bright lights

- very cold hands and feet

- seizures

- confusion/delirium

- extreme sleepiness/difficulty waking

Young people going on to university or college for the first time are particularly at risk of meningitis because they newly mix with so many other students, some of whom are unknowingly carrying the bacteria at the back of their nose and throat. 

There are numerous strains of the meningococcal infection.

There are numerous strains of the meningococcal infection. The MenACWY vaccination gives good protection against MenA, MenC, MenW, and MenY and is routinely offered to teenagers in school Years 9 and 10. However, this vaccine does not protect against all forms of meningococcal infection. Other strains such as MenB can circulate in young adults, which is why it’s important to know how to spot the symptoms of meningitis and sepsis as early detection and treatment can save lives. 

Further information on meningococcal disease 

Meningitis, The Meningitis Research Foundation, Monday to Friday, 9am to 5pm, UK: 080 8800 3344  -  Republic of Ireland: 1800 41 33 44  

Meningitis Now - 0808 80 10 388 (9am to 4pm Monday to Thursday and 9am to 1pm Friday)

Source: 

Link: https://www.gov.uk/government/news/expansion-of-meningitis-b-vaccination-offer-to-kent-students

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#Outbreak of invasive #meningococcal disease, SE #England - #Alert outlines recommended courses of action to manage cases with #infection and #contacts (#UKHSA, March 18 '26)

 

Invasive meningococcal disease: advice for the NHS in England

You may be aware of an evolving situation involving multiple cases of invasive meningococcal disease (IMD) reported among young people linked to the University of Kent and the Canterbury area. 

More information about IMD, signs and symptoms to look out for, and approaches to clinical and public health management are provided in the accompanying Briefing Note. 

The purpose of this CAS Alert is to outline priority steps that primary care and hospital clinicians should consider taking to manage suspected cases, potential contacts of cases, and to reduce the risk of infection spreading. 

Note that this is a rapidly evolving situation and we will update advice as further information emerges.

Epidemiology

-- Between 13 and 17 March 2026, UKHSA identified 20 cases of invasive meningococcal disease in the South East. 

-- Six cases have been confirmed as Neisseria meningitidis group B. 

-- Most cases are students from the University of Kent, Canterbury, and sixth form students from local secondary schools. 

-- At least 10 cases attended Club Chemistry in Canterbury on 5, 6 or 7 March 2026. 

-- The illness has been severe with rapid deterioration, and 2 deaths have occurred.

Management of cases

Infection prevention and control (IPC) and personal protective equipment (PPE)

-- For patients presenting with suspected meningococcal disease, standard infection prevention and control precautions should be followed in line with the National infection prevention and control manual for England (see Appendix 11). 

-- Use appropriate PPE (including Level 2 PPE where clinically indicated) for assessment and management of suspected IMD:

- clinical staff should apply standard respiratory hygiene and infection control measures in routine clinical settings

- wear a fluid resistant surgical facemask for routine care of patients with suspected invasive meningococcal disease

- wear an FFP3 mask or Hood for aerosol-generating procedures performed on patients with suspected invasive meningococcal disease

- continue transmission-based precautions until the patient has been established on antibiotics for at least 24 hours

- no additional or enhanced IPC measures are required beyond those recommended in national guidance

Immediate case management

-- Patients with IMD may present with septicaemia and/or meningitis. 

-- Meningococcal sepsis should be considered in a rapidly deteriorating patient with sepsis even in the absence of a non-blanching rash, which is usually a late sign. 

-- Clinicians should have a high index of suspicion where a young person aged 16 to 30 attends with consistent signs or symptoms.

-- In a community setting, rapid admission to hospital is the highest priority when IMD is suspected. Conveyance to hospital should not be delayed for procurement or administration of antibiotics.

-- In acute settings, patients with sepsis should be managed according to local sepsis guidelines and immediate clinical management should focus on stabilisation (including fluid resuscitation as appropriate) and early engagement with ITU colleagues where necessary.

-- Initial treatment recommendations are as follows (full treatment regimens will be commenced during hospital admission):

- Immediate single dose of IV/IM Ceftriaxone for suspected meningococcal infections (Ceftriaxone, Drugs, BNFC, NICE):

Age/weight / Dose

- adults - dose: 2g stat

- children with body weight 50kg and over or aged 9 years and older: dose 2g stat

- children up to 50kg body weight or aged under 9 years: dose 80 to 100 mg/kg (maximum per dose 4g)

Alternatively, immediate single dose of IV/IM Benzylpenicillin sodium for suspected meningococcal infections where it is not possible to administer Ceftriaxone (Benzylpenicillin sodium, Drugs, BNF, NICE):

Age / Dose

- adults and children aged 10 years or over: dose of 1.2g

- children aged 1 to 9 years: dose of 600mg

- children aged under 1 year: dose of 300mg

Information regarding clinical samples that should be taken for suspected IMD cases and referring meningococcal-positive clinical materials (including isolates, PCR-positive clinical samples and/or DNA extracts, and lysate extracted from Biofire loading syringes) to the National Meningococcal Reference Laboratory, is included in UKHSA national guidance.

Notifying UKHSA

-- All suspected cases of invasive meningococcal disease are statutorily notifiable by registered medical practitioners to the responsible UKHSA health protection team, without waiting for laboratory confirmation.

-- Notify UKHSA by contacting your health protection team.

Management of contacts

Informing contacts

-- Remind any presenting contacts of the signs and symptoms of meningococcal disease (meningitis and septicaemia) and the importance of seeking urgent medical attention if they have symptoms (even if prophylaxis has been taken). 

-- Early detection and treatment can save lives. 

-- The UKHSA South East Health Protection Team have provided warn and inform information to all cases and close contacts and are liaising closely with all educational and other community settings to provide advice.

Providing antibiotic chemoprophylaxis

-- Close contacts of confirmed or probable cases are being identified by UKHSA and require antibiotic prophylaxis. 

-- Timely chemoprophylaxis will prevent cases of disease and will save lives. 

-- Antibiotic prophylaxis should be given as soon as possible (ideally within 24 hours) after the diagnosis of the index case, regardless of vaccination status.

-- Eligibility is defined in national UKHSA and NICE CKS guidance.

-- This includes people who had the following forms of contact during the 7 days before onset of illness in the index case:

- people who have had prolonged close contact with the case in a household-type setting

- intimate kissing or equivalent close contact

- exposure to respiratory secretions (for example, mouth-to-mouth resuscitation)

- other close contacts identified through UKHSA risk assessment

-- In response to this outbreak, a wider group of contacts have been identified as requiring antibiotic prophylaxis on a precautionary basis:

- Students who live on the Canterbury campus at the University of Kent

- Staff who live or work in affected halls of residence blocks on the Canterbury campus at the University of Kent

- Staff members working at Club Chemistry nightclub, Canterbury, and anyone who attended the nightclub as visitors on 5, 6 or 7 of March 2026.

-- Local clinics are offering chemoprophylaxis to contacts in the Canterbury area. If an eligible close contact presents to a healthcare setting (primary or secondary care) and has not already received prophylaxis through UKHSA‑coordinated clinics, this should be prescribed for them.

-- As the outbreak evolves, further groups may be identified that require antibiotic prophylaxis and will be communicated with directly.

-- Where an eligible close contact presents and has not already received prophylaxis please prescribe this as per National guidance.

The first line treatment is ciprofloxacin: 

Ciprofloxacin dosage (for one dose) [note1]

-- All to be given as a single dose:

Age / Dose

- adults and children aged 12 years and over: 500 mg stat

- children aged 5 to 11 years: 250 mg stat

- children aged 1 to 4 years: 125 mg stat

- infants under 1 year [note 2]: 30 mg/kg to a maximum 125mg stat

Note 1. Ciprofloxacin suspension contains 250 mg/5ml.

Note 2. prescribed off-label. 

-- If ciprofloxacin is not suitable, alternatives are listed in the national guidance.

-- Where demand exceeds capacity, ICBs are responsible for ensuring timely access to post‑exposure prophylaxis and vaccination in line with NHS England commissioning guidance.

Advice concerning vaccination

-- Given the severity of the outbreak, and as an additional precautionary measure, a targeted vaccination programme will begin, starting with students that are residents of the Canterbury Campus Halls of Residence at the University of Kent who will be contacted directly. 

-- Precise details of eligibility will be confirmed by UKHSA. UKHSA will continue to assess ongoing risk to other populations and the programme may be extended.

Source: 

Link: https://www.gov.uk/guidance/outbreak-of-invasive-meningococcal-disease-south-east-england

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Empiric #azithromycin alters the upper respiratory #microbiome and #resistome without anti-inflammatory benefit in #COVID19

 

Abstract

Azithromycin is a widely used antibiotic and was frequently used to treat hospitalized patients during the COVID-19 pandemic. The impact of empiric azithromycin use on the respiratory microbiome in patients with viral respiratory infections is unclear. Here we used longitudinal metatranscriptomics on nasal swabs from a prospective multicentre cohort of 1,164 patients hospitalized for COVID-19. We compared the upper respiratory microbiome, resistome and systemic immune response in patients treated with azithromycin (n = 366) with those who received no antibiotics (n = 474) or other antibiotics (n = 324). We found that azithromycin altered microbiome composition and increased the expression and relative proportion of macrolide/lincosamide/streptogramin (MLS) resistance genes. These changes occurred after 1 day of exposure and persisted for over a week. MLS resistance gene expression was associated with commensals and potential pathogens, while there were no differences in host inflammatory gene expression in blood and airways. This demonstrates that empiric azithromycin treatment impacts the upper respiratory microbiome and resistome without apparent anti-inflammatory benefit.

Source: 

Link: https://www.nature.com/articles/s41564-026-02285-8

____

#UK, #England: Cases of invasive #meningococcal #disease notified in #Kent (UKHSA, March 16 '26)

 

From: UK Health Security Agency

Published: 16 March 2026

Last updated: 16 March 2026 

Update 16 March

The UK Health Security Agency (UKHSA) is continuing to investigate an outbreak of meningococcal disease in Kent with 13 cases notified since 13 March. Sadly, this includes 2 people who are known to have died.

Investigations have confirmed some of the cases visited Club Chemistry in Canterbury between 5 to 7 March prior to becoming unwell. UKHSA’s health protection team is working closely with the nightclub and partners including the University of Kent to limit the spread.

UKHSA is now advising anyone who visited Club Chemistry on 5 March, 6 March or 7 March to come forward for preventative antibiotic treatment as a precautionary measure. 

This can be collected from the following sites:

-- Senate Building at University of Kent, CT2 7NZ – open until 8pm on Monday 16 March (queue closes 7.15pm) and from 9am to 8pm on Tuesday 17 March.

-- Gate Clinic, Kent and Canterbury Hospital, Ethelbert Road, Canterbury, CT1 3NG - open until 8pm on Monday 16 March and planned to open from 8.30am to 7.30pm on Tuesday 17 March.

-- Westgate Hall, Westgate Hall Road, Canterbury, Kent, CT1 2BT. Planned to be open from 8.30am to 7.30pm on Tuesday 17 March.

-- Carey Building, Thanet Hub, Margate Northwood Rd, Westwood, Broadstairs, CT10 2WA. Planned to be open from 8.30am to 7.30 pm on Tuesday 17 March.

Advice has been issued to 16,000 staff and students at the University of Kent, where antibiotics are also being offered to those who need them.

Meningococcal disease can progress rapidly. Signs and symptoms of meningococcal meningitis and septicaemia can include:

- a fever, 

- headache, 

- rapid breathing, 

- drowsiness, 

- shivering, 

- vomiting, and 

- cold hands and feet. 

Septicaemia can also cause a characteristic rash that does not fade when pressed with a glass.

Early symptoms can often be confused with other illnesses such as a cold, flu or hangover, and students are particularly at risk of missing the early warning signs. If you or anyone you know develops any of these symptoms, seek medical help immediately by contacting a GP, calling NHS 111 or dialling 999 in an emergency. Knowing the signs and taking early treatment can be lifesaving.

Trish Mannes, UKHSA Regional Deputy Director for the South East, said:

''Our thoughts remain with the friends and family involved and we understand that many people in the university and wider community will be affected by this sad news.

''Our investigations have identified that some cases visited Club Chemistry in Canterbury and it is important that anyone who visited the club between 5 and 7 March now comes forward for preventative antibiotic treatment as a precaution, as well as those offered antibiotics at the university – these students are being contacted directly through the university.

''If you think you may have symptoms of meningitis, do not hesitate to seek medical help by contacting your GP or calling NHS 111.

Background

Meningococcal disease (meningitis and septicaemia) is an uncommon but serious disease caused by meningococcal bacteria. Very occasionally, the meningococcal bacteria can cause serious illness, (inflammation of the lining of the brain) and septicaemia (blood poisoning), which can rapidly lead to sepsis.

The onset of illness is often sudden and early diagnosis and treatment with antibiotics are vital.

Early symptoms, which may not always be present, include:

- a rash that doesn’t fade when pressed with a glass

- sudden onset of high fever

- severe and worsening headache

- stiff neck

- vomiting and diarrhoea

- joint and muscle pain

- dislike of bright lights

- very cold hands and feet

- seizures

- confusion/delirium

- extreme sleepiness/difficulty waking

Young people going on to university or college for the first time are particularly at risk of meningitis because they newly mix with so many other students, some of whom are unknowingly carrying the bacteria at the back of their nose and throat.

There are numerous strains of the meningococcal infection. The MenACWY vaccination gives good protection against MenA, MenC, MenW, and MenY. It is routinely offered to teenagers in school Years 9 and 10. However, this vaccine does not protect against all forms of meningococcal infection. Other strains such as MenB can circulate in young adults, which is why it’s important to know how to spot the symptoms of meningitis and septicaemia as early detection and treatment can save lives. 

Source: 

Link: https://www.gov.uk/government/news/cases-of-invasive-meningococcal-disease-confirmed-in-kent

____

#Macrolide #Resistance and P1 Cytadhesin Genotyping of #Mycoplasma pneumoniae during #Outbreak, #Canada, 2024–2025

 

Abstract

We investigated macrolide resistance and P1 genotypes of Mycoplasma pneumoniae during the 2024–2025 outbreak in Hamilton, Ontario, Canada. Macrolide resistance remained stable at ≈10%–20%, but significant shifts in P1 genotype distribution and resistance rates in P1 types occurred, indicating notable changes in M. pneumoniae molecular epidemiology in Ontario since 2011–2012.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/31/12/25-0872_article

____

Post #COVID19 #resurgence of #Mycoplasma pneumoniae infections in French #children (ORIGAMI): a retrospective and prospective multicentre cohort study

 

Summary

Background

Following a decline during the COVID-19 pandemic, Mycoplasma pneumoniae infections resurged in several countries. We aimed to characterise the clinical presentation of paediatric patients admitted to hospital for M pneumoniae during 2023 and 2024 in France.

Methods

We conducted a nationwide, multicentre, retrospective, and prospective observational study across 37 French paediatric hospitals (September, 2023–September, 2024). Children younger than 18 years who were hospitalised with laboratory-confirmed M pneumoniae infection (PCR or serology) were included. Demographics (excluding race), clinical features, laboratory and radiological findings, management, and outcomes data were described and analysed. Logistic regression was used to identify factors associated with paediatric intensive care unit (PICU) admission. The trial was registered at ClinicalTrials.gov (NCT06260371) and is complete.

Findings

We included 969 children and adolescents with M pneumoniae infection (7·3 years [SD 4·5], 426 [44%] of 966 patients were female and 540 [56%] of 966 were male). 936 (97%) of all patients were positive by PCR for M pneumoniae. Pneumonia was diagnosed in 628 (87%) of the 726 patients with respiratory involvement, and cutaneous manifestations were reported in 132 (14%) of 969 patients, including 56 (42%) of 132 who had erythema multiforme. Macrolides were prescribed in 884 (95%) of the 931 patients who were prescribed antibiotics, primarily azithromycin (563 [64%] of 884). Macrolide resistance was detected in one (5%) of the 21 tested samples. In total, 57 (6%) of 969 patients required PICU admission and four (<1%) died. Factors significantly associated with PICU admission included being older than 11 years (adjusted odds ratio 2·0 [95% CI 1·1–3·6]; p=0·023), asthma (2·2 [1·2–4·0]; p=0·0072), other underlying conditions (2·1 [1·2–3·7]; p=0·013), and erythema multiforme (3·7 [1·6–8·8]; 0·0025).

Interpretation

The 2023–2024 M pneumoniae epidemic in France resulted in a substantial paediatric hospitalisation burden. Although severe cases were uncommon, children older than 11 years, those with asthma, other comorbidities, and erythema multiforme were at increased risk of PICU admission. Ongoing surveillance and targeted management strategies are warranted for future epidemics.

Funding

Association Clinique et Thérapeutique Infantile du Val de Marne (ACTIV).

Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00598-5/abstract?rss=yes

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Host #Immunomodulatory Interventions in Severe #Influenza

 

Abstract

Currently, no immunomodulatory agents have been conclusively shown to benefit severe influenza. The World Health Organization conditionally advises against the use of systemic corticosteroids, macrolides, plasma therapy, mechanistic target of rapamycin inhibitors, and nonsteroidal anti-inflammatory drugs for such patients. High-dose systemic corticosteroids may increase mortality and morbidity in severe influenza; the potential of low-dose corticosteroids merits further study given survival benefits in patients with severe coronavirus disease 2019 (COVID-19). Passive immunotherapy using convalescent plasma or intravenous immunoglobulin (IVIG) from healthy donors has not proven effective, suggesting that future research should focus on hyperimmune plasma or IVIG from recent infections. An open-label randomized controlled trial (RCT) found that a triple combination of oseltamivir, clarithromycin, and naproxen improved outcomes in severe influenza. One RCT has indicated that sirolimus with corticosteroids can expedite liberation from mechanical ventilation and reduce viral load, warranting larger trials of sirolimus alone. In contrast, adding macrolides or nitazoxanide has not consistently improved clinical outcomes. Promising evidence exists for anti-C5a antibodies in COVID-19, while case reports hint that intravenous N-acetylcysteine may benefit severe influenza pneumonia. Observational data on statins remain conflicting. Further studies on COX-2 inhibitors in combination with antivirals and other immunomodulators are needed. Mycophenolic acid, pamidronate, and peroxisome proliferator-activated receptor gamma agonists are low priorities due to toxicity concerns. Research into human mesenchymal stromal cells and herbal medicine remains inconclusive. Overall, these findings support large-scale trials to validate promising results and address limitations in small studies. Treatment of severe influenza requires a multidisciplinary approach that integrates antiviral and immunomodulatory strategies. Clarifying these roles may enhance patient outcomes.

Source: Journal of Infectious Diseases, https://academic.oup.com/jid/article/232/Supplement_3/S262/8287912

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Genomic profiling of #cefotaxime-resistant #Haemophilus influenzae from #Norway and #Sweden reveals extensive expansion of virulent #MDR international clones

Abstract

Cefotaxime-resistant Haemophilus influenzae (CRHI) are a global concern, but little is known about their molecular epidemiology. The goal of this study was to perform genomic profiling of 191 CRHI from Norway (n = 183) or Sweden (n = 8) (2006–2018) and assess clonal spread using core genome multilocus sequence typing (cgMLST)-based Life Identification Number (LIN) codes based on whole genome sequencing (Ion Torrent). Cefotaxime resistance was confirmed with broth microdilution minimal inhibitory concentration (MIC), interpreted with the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. 35.7% of isolates with cefotaxime gradient MIC of 0.25 mg/L were falsely resistant. All but two isolates (blood) were non-invasive, and all but two (serotype f) were non-typeable. Characterization included calling of resistance determinants, ftsI typing (penicillin-binding protein 3, PBP3), and classification of PBP3-mediated beta-lactam resistance (rPBP3), with assignment to rPBP3 stage and group. All isolates had rPBP3-defining substitutions, and 78.5% were stage 3 (L389F positive). Beta-lactam MICs correlated well with rPBP3 genotypes. Significant proportions of stage 3 isolates were cross-resistant to ceftriaxone (86.0%) and meropenem (meningitis breakpoints, 26.0%). The CRHI prevalence in Norway doubled during the study period and approached 1%. A shift from stage 2 to stage 3 rPBP3 in 2011–2012 led to emergence of CRHI with higher beta-lactam MICs and co-resistance to multiple non-beta-lactams, including extensively drug-resistant (XDR) strains. The shift was driven by transformation with two distinct variants of the transpeptidase region and multiclonal expansion. 66.0% of the isolates belonged to 27 clusters. Ten clusters or singletons belonged to international CRHI clones represented in the PubMLST database. The study provides new insight into CRHI evolution, resistance profiles, and clonal dynamics in a period when this phenotype went from exceptional to unusual in Europe. International CRHI clones are described for the first time, including eight high-risk clones associated with invasive disease, calling for enhanced genomic surveillance. LIN coding, supplemented with ftsI typing and rPBP3 staging, is well-suited for definition of CRHI clones. LIN9, defined by ≤ 10 allelic differences, offered the highest resolution level fully supported by maximum likelihood core genome phylogeny and is proposed as a global standard for genomic surveillance of H. influenzae.

Source: Frontiers in Microbiology, https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2025.1601390/full

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#Corynebacterium diphtheriae #Outbreak in #Migrant Populations in #Europe

Abstract

Background

A surge of cases of Corynebacterium diphtheriae infection was observed in reception centers for migrants in Europe beginning in the summer of 2022. Most of the cases were cutaneous, although some respiratory cases as well as one death were reported. A pan-European consortium was created to assess the clinical, epidemiologic, and microbiologic features of this outbreak.

Methods

We assessed cases of toxigenic C. diphtheriae infection that were reported in 10 European countries from January through November 2022. Data regarding countries of origin and transit routes were obtained from interviews with the patients. Whole-genome sequencing and antimicrobial-susceptibility testing were performed on bacterial isolates that were obtained from the patients. The phylogenetic relationships of the isolates and their antimicrobial-resistance genes were evaluated.

Results

A total of 363 toxigenic C. diphtheriae isolates were identified among 362 patients during the study period. Clinical data were available for 346 patients (95.6%): 268 (77.5%) had cutaneous diphtheria, 53 (15.3%) had respiratory diphtheria (11 [3.2%] had a pseudomembrane), and 9 (2.6%) had both respiratory and cutaneous symptoms. Four major genetic clusters were identified, which indicated the multiclonal nature of the outbreak. The ermX gene (which codes for erythromycin resistance) and the pbp2m and blaOXA-2 genes (which code for beta-lactam resistance) were detected in a subgroup of isolates. Isolates that carried ermX were resistant to erythromycin, and isolates that carried pbp2m were resistant to penicillin but were susceptible to amoxicillin. On the basis of the genomic variation within the four genetic clusters, their most recent common ancestors were estimated to have existed between 2017 and 2020.

Conclusions

The distribution of each genetic cluster of C. diphtheriae isolates across multiple countries in Europe showed repeated cross-border spread. The large number of C. diphtheriae infections among migrants is a cause for concern, particularly given that antimicrobial-resistance phenotypes threaten the efficacy of first-line treatments. (Funded by the Bavarian State Ministry of Health, Care, and Prevention and others.)

Source: The New England Journal of Medicine, https://www.nejm.org/doi/full/10.1056/NEJMoa2311981?query=TOC

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#SARS-CoV-2 infection #enhancement by #amphotericin B: implications for disease management

ABSTRACT

Severe coronavirus disease 2019 (COVID-19) patients who require hospitalization are at high risk of invasive pulmonary mucormycosis. Amphotericin B (AmB), which is the first-line therapy for invasive pulmonary mucormycosis, has been shown to promote or inhibit replication of a spectrum of viruses. In this study, we first predicted that AmB and nystatin had strong interactions with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins using in silico screening, indicative of drugs with potential therapeutic activity against this virus. Subsequently, we investigated the impact of AmB, nystatin, natamycin, fluconazole, and caspofungin on SARS-CoV-2 infection and replication in vitro. Results showed that AmB and nystatin actually increased SARS-CoV-2 replication in Vero E6, Calu-3, and Huh7 cells. At optimal concentrations, AmB and nystatin increase SARS-CoV-2 replication by up to 100- and 10-fold in Vero E6 and Calu-3 cells, respectively. The other antifungals tested had no impact on SARS-CoV-2 infection in vitro. Drug kinetic studies indicate that AmB enhances SARS-CoV-2 infection by promoting viral entry into cells. Additionally, knockdown of genes encoding for interferon-induced transmembrane (IFITM) proteins 1, 2, and 3 suggests AmB enhances SARS-CoV-2 cell entry by overcoming the antiviral effect of the IFITM3 protein. This study further elucidates the role of IFITM3 in viral entry and highlights the potential dangers of treating COVID-19 patients, with invasive pulmonary mucormycosis, using AmB.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.00519-25?af=R

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#Phage-induced #protection against lethal #bacterial #reinfection

Significance

In 2021, antimicrobial-resistant bacteria were responsible for 1.14 million deaths and associated with 4.71 million deaths globally. Patients who experience sepsis often face a higher risk of reinfections and hospital readmissions. To combat this crisis, bacteriophages—viruses that infect and kill bacteria—are regaining interest as a potential solution. Here, we show that mice infected with extraintestinal pathogenic Escherichia coli and treated with phage HP3 not only recover from the initial infection but also gain protection against a secondary challenge with the same bacterial strain. The protective effect is dependent on the bacteriolytic action of the phage. These findings shift phages from being solely therapeutic antimicrobials to dual-action immunotherapeutics capable of both clearing and preventing bacterial infections.

Abstract

Bacteriophages, or phages, are viruses that target and infect bacteria. Due to a worldwide rise in antimicrobial resistance (AMR), phages have been proposed as a promising alternative to antibiotics for the treatment of resistant bacterial infections. Up to this point in history, phage use in preclinical animal studies, clinical trials, and emergency-use compassionate care cases has centered around the original observation from 1915 showing phage as lytic agent, and thus a treatment that kills bacteria. Here, we describe an activity associated with phage therapy that extends beyond lytic activity that results in long-term protection against reinfection. This activity is potent, providing almost complete protection against a second lethal infection for animals treated with phage therapy. The activity also reduced infection burden an astounding billion-fold over the control. Reinfection protection requires phage lytic killing of its target bacterium but is independent of additional phage therapy. The effect is not driven by phage alone, lingering phage resistors, or a sublethal inoculum. In vitro phage-lysed bacteria provide partial protection, suggesting a combination of phage-induced lytic activity and immune stimulation by phage treatment is responsible for the effect. These observations imply certain phages may induce host adaptive responses following the lysis of the infecting bacteria. This work suggests phage therapy may contain a dual-action effect, an initial treatment efficacy followed by a long-term protection against reoccurring infection, a therapeutic-vaccination mechanism of action.

Source: Proceedings of the National Academy of Sciences of the United States of America, https://www.pnas.org/doi/abs/10.1073/pnas.2423286122?af=R

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The #WHO #Bacterial Priority #Pathogens #List 2024: a prioritisation study to guide research, development, and public health strategies against antimicrobial resistance

Summary

Background

The 2017 WHO Bacterial Priority Pathogens List (BPPL) has been instrumental in guiding global policy, research and development, and investments to address the most urgent threats from antibiotic-resistant pathogens, and it is a key public health tool for the prevention and control of antimicrobial resistance (AMR). Since its release, at least 13 new antibiotics targeting bacterial priority pathogens have been approved. The 2024 WHO BPPL aims to refine and build on the previous list by incorporating new data and evidence, addressing previous limitations, and improving pathogen prioritisation to better guide global efforts in combating AMR.

Methods

The 2024 WHO BPPL followed a similar approach to the first prioritisation exercise, using a multicriteria decision analysis framework. 24 antibiotic-resistant bacterial pathogens were scored based on eight criteria, including mortality, non-fatal burden, incidence, 10-year resistance trends, preventability, transmissibility, treatability, and antibacterial pipeline status. Pathogens were assessed on each of the criteria on the basis of available evidence and expert judgement. A preferences survey using a pairwise comparison was administered to 100 international experts (among whom 79 responded and 78 completed the survey) to determine the relative weights of the criteria. Applying these weights, the final ranking of pathogens was determined by calculating a total score in the range of 0–100% for each pathogen. Subgroup and sensitivity analyses were conducted to assess the impact of experts’ consistency, background, and geographical origin on the stability of the rankings. An independent advisory group reviewed the final list, and pathogens were subsequently streamlined and grouped into three priority tiers based on a quartile scoring system: critical (highest quartile), high (middle quartiles), and medium (lowest quartile).

Findings

The pathogens’ total scores ranged from 84% for the top-ranked bacterium (carbapenem-resistant Klebsiella pneumoniae) to 28% for the bottom-ranked bacterium (penicillin-resistant group B streptococci). Antibiotic-resistant Gram-negative bacteria (including K pneumoniae, Acinetobacter spp, and Escherichia coli), as well as rifampicin-resistant Mycobacterium tuberculosis, were ranked in the highest quartile. Among the bacteria commonly responsible for community-acquired infections, the highest rankings were for fluoroquinolone-resistant Salmonella enterica serotype Typhi (72%), Shigella spp (70%), and Neisseria gonorrhoeae (64%). Other important pathogens on the list include Pseudomonas aeruginosa and Staphylococcus aureus. The results of the preferences survey showed a strong inter-rater agreement, with Spearman's rank correlation coefficient and Kendall's coefficient of concordance both at 0·9. The final ranking showed high stability, with clustering of the pathogens based on experts’ backgrounds and origins not resulting in any substantial changes to the ranking.

Interpretation

The 2024 WHO BPPL is a key tool for prioritising research and development investments and informing global public health policies to combat AMR. Gram-negative bacteria and rifampicin-resistant M tuberculosis remain critical priority pathogens, underscoring their persistent threat and the limitations of the current antibacterial pipeline. Focused efforts and sustained investments in novel antibacterials are needed to address AMR priority pathogens, which include high-burden antibiotic-resistant bacteria such as Salmonella and Shigella spp, N gonorrhoeae, and S aureus. Beyond research and development, efforts to address these pathogens should also include expanding equitable access to existing drugs, enhancing vaccine coverage, and strengthening infection prevention and control measures.

Source: Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00118-5/fulltext?rss=yes

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