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What's new in infectious disease?
Infection Control
Uncertain role of systemic antibiotics to prevent ventilator-associated pneumonia
(December 2024)
Ventilator-associated pneumonia (VAP) is a major cause of death in ICU patients. A recent randomized trial involving patients with moderate or severe traumatic brain injury (TBI) or acute stroke found that administering 2 g of ceftriaxone intravenously within 12 hours of intubation reduced the 7-day VAP rate (14% vs. 32%) and 28-day mortality rate (15% vs. 25%) compared to a placebo, without causing significant adverse effects.
14%
32%
Ceftriaxone
Placebo
VAP Rate
15%
25%
Ceftriaxone
Placebo
Mortality Rate
However, a subsequent meta-analysis that included this trial along with six others involving over 800 patients with acute brain injuries (such as stroke, TBI, or post-cardiac arrest) showed that while a short course of peri-intubation IV antibiotics lowered VAP incidence, it did not significantly affect ventilator-free days, ICU stay duration, or in-hospital mortality.
Due to these mixed findings, practices differ among experts. While some avoid routine systemic antibiotics for VAP prevention due to concerns about antibiotic resistance, others recommend a single peri-intubation dose of ceftriaxone for patients at high risk, such as those with acute TBI.
Summaries of various published medical studies
Genetic characterization of Haemophilus ducreyi from non-genital skin lesions in Cameroon BACTERIA AND BACTERIAL DISEASES
Volume 90, Issue 3106448 March 2025
Haemophilus ducreyi, historically known as the primary cause of chancroid, a genital ulcer disease, is now increasingly linked to cutaneous ulcers in regions where yaws is prevalent, such as the South Pacific, Southeast Asia, and Sub-Saharan Africa. Although this bacterium plays a significant role in these conditions, detailed genetic data and tools for studying its characteristics are limited.
In this study, researchers employed PCR-based genetic analysis to investigate H. ducreyi, confirming its involvement in cutaneous ulcers. Due to the difficulty in culturing this bacterium, whole genome sequencing (WGS) and non-culture methods were employed for diagnosis and analysis. Antibiotic susceptibility testing of cultured isolates demonstrated that H. ducreyi was sensitive to ceftriaxone, azithromycin, and ciprofloxacin.
Using multilocus sequence typing (MLST) data from both WGS and direct clinical samples, 38 complete profiles were identified across six loci. This included 34 profiles derived from clinical samples and four from cultured isolates, resulting in the identification of 14 unique sequence types (STs). BURST analysis grouped these STs into two distinct clonal complexes. Additionally, a genetic variation was observed in the ftsI gene, which encodes penicillin-binding protein.
Recent safety warnings for anti-infective treatments
Antimicrobial Resistance
KEY FACTS
Antimicrobial resistance (AMR) is one of the top global public health and development threats. It is estimated that bacterial AMR was directly responsible for 1.27 million global deaths in 2019 and contributed to 4.95 million deaths (1).
The misuse and overuse of antimicrobials in humans, animals and plants are the main drivers in the development of drug-resistant pathogens.
AMR affects countries in all regions and at all income levels. Its drivers and consequences are exacerbated by poverty and inequality, and low- and middle-income countries are most affected.
AMR puts many of the gains of modern medicine at risk. It makes infections harder to treat and makes other medical procedures and treatments – such as surgery, caesarean sections and cancer chemotherapy – much riskier.
The world faces an antibiotics pipeline and access crisis. There is an inadequate research and development pipeline in the face of rising levels of resistance, and urgent need for additional measures to ensure equitable access to new and existing vaccines, diagnostics and medicines.The world faces an antibiotics pipeline and access crisis. There is an inadequate research and development pipeline in the face of rising levels of resistance, and urgent need for additional measures to ensure equitable access to new and existing vaccines, diagnostics and medicines.
In addition to death and disability, AMR has significant economic costs. The World Bank estimates that AMR could result in US$ 1 trillion additional healthcare costs by 2050, and US$ 1 trillion to US$ 3.4 trillion gross domestic product (GDP) losses per year by 2030 (2).
Priorities to address AMR in human health include preventing all infections, which may result in inappropriate use of antimicrobials; ensuring universal access to quality diagnosis and appropriate treatment of infections; and strategic information and innovation, for example surveillance of AMR and antimicrobial consumption/use, and research and development for novel vaccines, diagnostics and medicines.
Insights on new clinical trials and their implications
Macrolide-Resistant Mycoplasma pneumoniae Infections among Children after COVID-19 Pandemic, Ohio, USA
Volume 31, Number 3
March 2025
Mycoplasma pneumoniae is a common cause of community-acquired respiratory infections in school-aged children, responsible for 10%–40% of pneumonia cases requiring hospitalization. This pathogen is present globally, with periodic outbreaks occurring every few years.
During the COVID-19 pandemic, public health measures aimed at controlling SARS-CoV-2 transmission also significantly reduced M. pneumoniae activity. At Nationwide Children’s Hospital (NCH) in Columbus, Ohio, nearly no cases were reported during this period. However, since the fall of 2023, M. pneumoniae infections have resurged globally. In central Ohio, this reemergence began in September 2023, followed by a sharp increase during the summer of 2024.
Macrolides are the primary treatment for M. pneumoniae infections. Resistance to macrolides occurs due to point mutations in the V region of the 23S rRNA gene, which disrupt bacterial protein synthesis. The most common mutation, A2063G, accounts for over 95% of resistant variants in the United States, alongside the A2064G mutation.
Between 2015 and 2018, macrolide-resistant M. pneumoniae (MRMp) rates in the United States ranged from 2.1% to 18.3%. During that same period, NCH reported a 2.8% MRMp rate among its pediatric patients. With the recent resurgence of M. pneumoniae, efforts are underway to assess the current rate of macrolide resistance in children in central Ohio.
Risk mitigation strategies for enhanced patient safety
GOLD 2025 REPORT
The GOLD 2025 Report provides a comprehensive update on the diagnosis, assessment, and management of Chronic Obstructive Pulmonary Disease (COPD).
Introduction and Taxonomy of COPD
COPD is a heterogeneous disease with various etiotypes, or subtypes based on causes. The report proposes a taxonomy for COPD, categorizing it into different types based on genetic, developmental, and environmental factors. These include genetically determined COPD (COPD-G), which includes Alpha-1 antitrypsin deficiency (AATD) and other genetic variants; COPD due to abnormal lung development (COPD-D), linked to early life events like premature birth and low birthweight; and environmental COPD, which includes cigarette smoking COPD (COPD-C), biomass and pollution exposure COPD (COPD-P), COPD due to infections (COPD-I), COPD and asthma (COPD-A), and COPD of unknown cause (COPD-U). This taxonomy highlights the need for tailored therapies for different COPD subtypes.
Diagnosis and Assessment
A diagnosis of COPD should be considered in patients with dyspnea, chronic cough, sputum production, or a history of risk factors. However, spirometry showing a post-bronchodilator FEV1/FVC ratio < 0.7 is mandatory for diagnosis. The goals of the initial COPD assessment are to determine the severity of airflow obstruction, the impact on health status, and the risk of future events such as exacerbations, hospitalizations, and death. COPD patients often have other chronic diseases, including cardiovascular disease, osteoporosis, and depression, which should be actively sought and treated.
Chronic dyspnea is the most characteristic symptom of COPD, often accompanied by cough and sputum production. Symptoms may vary daily and can precede airflow obstruction by years. Dyspnea is a major cause of disability in COPD, described as increased effort to breathe, chest heaviness, or air hunger. It is prevalent across all stages of COPD and is influenced by multiple factors, including respiratory mechanics, gas exchange abnormalities, and psychological distress. Chronic cough is often the first symptom, initially intermittent but may become daily. It can be productive or non-productive. Regular sputum production for three or more months in two consecutive years is a classical definition of chronic bronchitis. Wheezing and chest tightness may vary daily and are not exclusive to COPD. Fatigue is a common and distressing symptom, impacting daily activities and quality of life. In severe COPD, weight loss, muscle mass loss, and anorexia are common and have prognostic importance.
COPD can be difficult to distinguish from asthma, but other conditions like congestive heart failure, bronchiectasis, tuberculosis, and obliterative bronchiolitis are easier to differentiate. A detailed medical history should include exposure to risk factors, past medical history, family history, pattern of symptom development, history of exacerbations, presence of comorbidities, and the impact of the disease on the patient’s life.
Spirometry and Lung Function Testing
Forced spirometry is the most reproducible and objective measurement of airflow obstruction. It is a noninvasive, reproducible, and readily available test. Spirometry measures the volume of air forcibly exhaled from the point of maximal inspiration (forced vital capacity, FVC), the volume of air exhaled during the first second of this maneuver (forced expiratory volume in one second, FEV1), and the ratio of these two measurements (FEV1/FVC). Spirometry measurements are evaluated by comparison with reference values based on age, height, and sex.
Post-bronchodilator spirometry is required for the diagnosis and assessment of COPD. Pre-bronchodilator spirometry can be used as an initial test to investigate whether symptomatic patients have airflow obstruction. If the pre-bronchodilator spirometry does not show obstruction, performing post-bronchodilator spirometry is not necessary unless there is a very high clinical suspicion of COPD. The spirometric criterion for airflow obstruction selected by GOLD for the diagnosis of COPD remains a post-bronchodilator ratio of FEV1/FVC < 0.7. This criterion is simple and independent of reference values, but it may result in over-diagnosis in the elderly and under-diagnosis in younger adults.
Assessment of Symptoms and Exacerbation Risk
Because there is only a weak correlation between the severity of airflow obstruction and the symptoms experienced by the patient, formal assessment of symptoms using validated questionnaires is required. The modified Medical Research Council (mMRC) dyspnea scale is a simple questionnaire that measures breathlessness, a key symptom in many patients with COPD. Multidimensional questionnaires, such as the COPD Assessment Test (CAT™) and the St. George’s Respiratory Questionnaire (SGRQ), are recommended for a more comprehensive assessment of health status.
Exacerbations of COPD (ECOPD) are episodes of acute respiratory symptom worsening often associated with increased local and systemic inflammation. ECOPD are key events in the natural history of the disease because they impact significantly on the health status of the patient, enhance the rate of lung function decline, worsen the prognosis, and are associated with most of the healthcare costs of COPD. The best predictor of having frequent exacerbations is the previous history of exacerbations.
Blood Eosinophil Count and Biomarkers
Blood eosinophil counts predict the magnitude of the effect of inhaled corticosteroids (ICS) in preventing future exacerbations. Higher blood eosinophil counts in COPD patients are associated with increased lung eosinophil numbers and the presence of higher levels of markers of type-2 inflammation in the airways. Blood eosinophil counts can help clinicians estimate the likelihood of a beneficial preventive response to the addition of ICS to regular bronchodilator treatment.
Multimorbidity and Cardiovascular Risk
People with COPD often suffer other concomitant chronic diseases (multimorbidity), including cardiovascular disease, metabolic syndrome, osteoporosis, depression, and anxiety. Multimorbidity influences mortality and hospitalizations independently of the severity of airflow obstruction. Cardiovascular diseases are a prominent cause of death in COPD, particularly in patients with mild-moderate airflow obstruction. The mechanisms underlying the frequent co-existence of COPD and cardiovascular diseases are multiple, including shared risk factors, systemic inflammation, abnormal pulmonary gas exchange, and reduced physical activity.
Additional Investigations
In cases where there is a marked discordance between the level of airflow obstruction and the perceived symptoms, a more detailed evaluation should be carried out to better understand lung mechanics, lung structure, and comorbidities. Physiological tests, such as lung volumes and carbon monoxide diffusing capacity of the lungs (DLco), can help characterize the severity of COPD. Exercise testing and assessment of physical activity can reveal severe constraints in patients with minimal symptoms. Imaging, including chest X-ray and computed tomography (CT), can provide insights into the structural and pathophysiologic abnormalities present in COPD.
Screening and Case-Finding
The role of screening spirometry for the diagnosis of COPD in the general population is controversial. In asymptomatic individuals without significant exposures to tobacco or other risk factors, screening spirometry is probably not indicated. However, in those with symptoms or risk factors, spirometry should be considered as a method for early case finding. Case-finding tools that incorporate exposures, symptoms, and healthcare utilization have been developed and can identify previously undiagnosed COPD.
Leveraging Lung Cancer Imaging for COPD Screening
Annual low-dose CT (LDCT) imaging of the chest is recommended for lung cancer screening in individuals aged 50 to 80 years with a ≥ 20 pack-year smoking history. Lung cancer and COPD share common risk factors, and COPD is also an independent risk factor for lung cancer. Thoroughly assessing symptoms and performing spirometry in individuals undergoing LDCT for lung cancer screening represents a unique opportunity to simultaneously screen patients for both the presence of unrecognized symptoms of COPD and airflow obstruction.
Conclusion
The GOLD 2025 Report emphasizes the importance of a comprehensive approach to the diagnosis, assessment, and management of COPD. It highlights the heterogeneity of the disease and the need for tailored therapies based on different etiotypes.
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