Bacterial Pneumonia Research Articles

Bacteriology of Aspiration Pneumonia: The Lung Microbiome and the Changing Microbial Etiology.

Aspiration pneumonia refers to the process of alveolar inflammation induced by the inhalation of oropharyngeal secretions into the lower respiratory tract. Predisposing factors comprise swallowing dysfunction, impaired cough reflex, and degenerative neurological diseases. Accumulating evidence projects a fading contribution of anaerobic bacteria in aspiration pneumonia at the expense of Gram-negative bacilli, with Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa, becoming the predominant organisms recovered from respiratory specimens. Aspiration of oropharyngeal secretions colonized with respiratory pathogens induces a profound disequilibrium of the lung microbiota resulting in a state of dysbiosis. Understanding this complex temporal variability between microbiome-host associations was only made possible with the introduction of metagenomic sequencing. In this narrative review, we summarize existing knowledge and elaborate on the evolving microbiology of aspiration pneumonia including the link between oral microbiome and pulmonary aspiration. We also highlight the progress and challenges in instituting microbiome-targeted strategies for preventing and treating the sequelae of aspiration pneumonia.

Enhancing multiclass COVID-19 prediction with ESN-MDFS: Extreme smart network using mean dropout feature selection technique.

Deep learning and artificial intelligence offer promising tools for improving the accuracy and efficiency of diagnosing various lung conditions using portable chest x-rays (CXRs). This study explores this potential by leveraging a large dataset containing over 6,000 CXR images from publicly available sources. These images encompass COVID-19 cases, normal cases, and patients with viral or bacterial pneumonia. The research proposes a novel approach called "Enhancing COVID Prediction with ESN-MDFS" that utilizes a combination of an Extreme Smart Network (ESN) and a Mean Dropout Feature Selection Technique (MDFS). This study aimed to enhance multi-class lung condition detection in portable chest X-rays by combining static texture features with dynamic deep learning features extracted from a pre-trained VGG-16 model. To optimize performance, preprocessing, data imbalance, and hyperparameter tuning were meticulously addressed. The proposed ESN-MDFS model achieved a peak accuracy of 96.18% with an AUC of 1.00 in a six-fold cross-validation. Our findings demonstrate the model's superior ability to differentiate between COVID-19, bacterial pneumonia, viral pneumonia, and normal conditions, promising significant advancements in diagnostic accuracy and efficiency.

Abstract 4135700: Effects of Mitochondrial Dysfunction on Extracellular Vesicle Release and Subsequent Disruption of the Lung Vascular Endothelial Barrier

Background: Lung endothelial cell (EC) barrier disruption is a hallmark of acute lung injury (ALI), which is commonly caused by bacterial pneumonia. Alveolar epithelial cells (AEC) are the first line of defence against invading respiratory pathogens in the lungs and can mediate inflammatory signaling to the adjacent EC contributing to barrier disruption. We have previously demonstrated that pneumolysin (PLY), a major Streptococcus pneumoniae virulence factor, induces both mitochondrial dysfunction in lung AEC and release of large extracellular vesicles (EVs). These EVs, which are enriched with mitochondrial cargo, contribute to increased permeability of the lung EC barrier. Here, we investigate strategies to inhibit mitochondrial dysfunction in AEC and examine how these interventions impact EC barrier function. Methods: Human alveolar epithelial cells (A549) or immortalized AEC (Cell Biologics) were pre-treated with mitoTEMPO (mtROS scavenger), P110 (excessive fission inhibitor), or ensifentrine [dual phosphodiesterase (PDE) 3/4 inhibitor] prior to PLY treatment (100-300 ng/ml, 4 hrs). Mitochondrial function was assessed by the JC-1 assay. EVs were isolated from cell media and analyzed for their mitochondrial content (Tom20 and Tim23 expression). To assess their functional role, EVs were added to TNF-α treated human lung microvascular EC, and barrier function was then determined using the ECIS assay to measure transendothelial electrical resistance (TER). Results: PLY-induced mitochondrial dysfunction was reduced in the presence of mitoTempo or P110. EVs from PLY-treated AEC (EV PLY ; enriched mitochondrial content) exacerbated TNF-α-induced EC barrier permeability as indicated by the significant decrease in TER. EV PLY derived from MitoTEMPO or P110-pretreated AEC contained less mitochondrial cargo and resulted in less EC permeability after TNF-α. Compared to mitoTEMPO and P110, ensifentrine exhibited superior protection against mitochondrial dysfunction after PLY exposure. In addition, in the presence of ensifentrine, the quantity of EV release and their extracelllular mitochondrial content were both dramatically reduced. In contrast to control EV PLY , EV PLY from ensifentrine-pretreated AEC demonstrated no barrier disruptive properties. Conclusions: Mitochondrial dysfunction in AEC contributes to vascular endothelial injury in ALI through mechanisms involving the release of barrier-disruptive EVs, which can be effectively targeted by inhibiting PDE3/4.

A Mucous Permeable Local Delivery Strategy Based on Manganese-Enhanced Bacterial Cuproptosis-like Death for Bacterial Pneumonia Treatment.

Bacterial pneumonia is one of the most challenging global infectious diseases with high morbidity and mortality. Considering the antibiotic abuse and resistance of bacterial biofilms, a variety of metal-based materials have been developed. However, due to the high oxygen environment of the lungs, some aerobic infection bacteria have high tolerance to oxygen and ROS, and most of the metal-based materials based on ROS may not achieve good therapeutic effects. Inspired by the sensitivity of cuproptosis to aerobic respiratory cells, we designed a copper composite antibacterial nanoparticle and found that it can effectively induce cuproptosis-like death in the aerobic bacteria of the lungs. To address the challenge of in vivo application of cuproptosis, manganese dioxide was first incorporated to deplete protective glutathione, which can interact with copper and thus hinder the interaction of copper with proteins and assist in antibacterial action through immune enhancement. Cuproptosis-like death also requires a large number of copper ions. To meet this demand, we deliver positively hydrophilic modified composite nanoparticles that effectively penetrate the lung mucus layer directly to the lungs through local administration, and the copper ions are further released rapidly by the acidic environment at the infected site, which can further destroy bacterial biofilms in synergy with manganese. This drug-delivery system can effectively treat pneumonia caused by aerobic bacteria and avoid systemic toxicity that can be caused by large doses of copper.

Impella 5.5 as a bridge-to-surgery in acute ischemic mitral regurgitation post-percutaneous coronary intervention: a case report

BackgroundAcute ischemic mitral regurgitation (AIMR) is a significant complication of acute coronary syndrome that leads to severe and immediate hemodynamic deterioration and cardiogenic shock. Intra-aortic balloon pumps (IABP) are commonly used to support patients with AIMR as a bridge to surgery, though they may be insufficient in some cases.Case PresentationA 74-year-old male presented with two days of indigestion and evident hypoxia, and an electrocardiogram revealed inferior and lateral ST-elevation myocardial infarction. Angiography demonstrated severe two-vessel coronary disease with a 100% thrombotic occlusion of the second obtuse marginal artery (OM2, culprit lesion) and an 80% stenosis of the proximal left anterior descending artery (LAD). Despite stenting of OM2, the patient remained hypoxic and hypotensive, necessitating escalated support via an IABP. A follow-up echocardiogram revealed severe mitral regurgitation presumed to be AIMR secondary to a ruptured posteromedial papillary muscle with a flail anterior leaflet (A2). Despite aggressive supportive measures with the IABP, the patient’s hemodynamics continued to show cardiogenic shock and clinical status did not improve. However, the patient was required to abstain from surgery for a P2Y12 inhibitor therapy wash out period. Consequently, the IABP was upgraded to Impella 5.5 as bridge-to-surgery support on day 1 post-admission. Subsequently, the patient’s hemodynamics improved, and he underwent a combined mitral valve replacement and coronary artery bypass grafting surgery on day 7 post-admission without incident. The Impella was successfully explanted on day 25 post-admission. Delay in explant was due to hypotension and respiratory status despite normalizing hemodynamics and echocardiogram revealing recovered left ventricular ejection fraction. The patient developed bacterial pneumonia and acute respiratory distress syndrome and expired on day 27 post-admission.ConclusionAlthough IABP is standard for supporting AIMR patients as a bridge to surgery, it may not provide sufficient hemodynamic support. This case supports a growing body of evidence that alternative forms of hemodynamic support should be considered if the traditional therapeutic modalities for AIMR do not adequately support patients. Clinicians may consider upgrading IABP to Impella to provide increased hemodynamic support and maintain AIMR patient stability while awaiting cardiac surgery.

Streptococcus pneumoniae serotype distribution in Bangladeshi under-fives with community-acquired pneumonia pre-10-valent pneumococcal conjugate vaccination

BackgroundStreptococcus pneumoniae is the most frequent causative pathogen of bacterial pneumonia in children worldwide. Bangladesh introduced the 10-valent pneumococcal conjugate vaccine (PCV10) in their national immunization program for infants in 2015. We assessed its potential coverage in under-fives with community-acquired pneumonia (CAP) in the years before PCV10 was introduced.MethodsA total of 1502 childhood pneumonia cases (< 5 year olds living in the urban section Kamalapur, Dhaka) were enrolled between 2011 and 2013. Acute phase and late (convalescent) serum samples were collected from 1380 cases. Serotype-specific pneumococcal antibody concentrations were measured using a 25-plex immunoassay panel. Pneumococcal CAP was diagnosed based on a serotype-specific pneumococcal antibody response.ResultsS. pneumoniae was serologically identified as causative pathogen in 406/1380 (29%) cases. The five most prevalent serotypes were (in descending order) 11A, 22F, 3, 2 and 19F. Based on the percentage of pneumonia cases associated with PCV10 vaccine types, the potential PCV10 coverage was 29% (116/406).ConclusionsIn almost a third of the studied cases S. pneumoniae was identified as a causative pathogen. Because of the characteristics of the immunoassay, this might well be a gross underestimation. Nevertheless, the potential PCV10-coverage was low. Given the high serotype diversity, the region might benefit greatly from a higher-coverage PCV or recombinant protein vaccine.

Mucus-Penetrable Biomimetic Nanoantibiotics for Pathogen-Induced Pneumonia Treatment.

Bacterial pneumonia has garnered significant attention in the realm of infectious diseases owing to a surge in the incidence of severe infections coupled with the growing scarcity of efficacious therapeutic modalities. Antibiotic treatment is still an irreplaceable method for bacterial pneumonia because of its strong bactericidal activity and good clinical efficacy. However, the mucus layer forming after a bacterial infection in the lungs has been considered as the "Achilles' heels" facing the clinical application of such treatment. Herein, traceable biomimetic nanoantibiotics (BioNanoCFPs) were developed by loading indacenodithieno[3,2-b]thiophene (ITIC) and cefoperazone (CFP) in nanoplatforms coated with natural killer (NK) cell membranes. The BioNanoCFP exhibited excellent demonstrated mucus-penetrating abilities, facilitating their arrival at the infection site. The presence of Toll-like receptors in the NK cell membrane rendered the BioNanoCFP with the capability to recognize pathogen-associated molecular patterns within bacteria, allowing precise targeting of bacterial colonization sites and achieving substantial therapeutic efficacy. Overall, our findings demonstrate the viability and desirability of using NK cell membrane-mediated drug delivery as a promising strategy for precision treatment.

Flexible Development Programs for Antibacterial Drugs to Address Unmet Medical Needs.

The US Food and Drug Administration recognizes the unmet medical need for antibacterial drugs to treat serious bacterial diseases caused by resistant pathogens for which effective therapies are limited or lacking. The agency also recognizes that designing and conducting clinical trials to assess the safety and efficacy of drugs to treat resistant infections is challenging, especially for drugs only active against a single or a few bacterial species, and that a more flexible development program might be appropriate. In this article, we discuss several regulatory considerations for flexible development programs for antibacterial drugs intended to meet an unmet medical need. As an example, we use the recent approval of sulbactam for injection and durlobactam for injection (XACDURO) for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex.

γδ T Cells Mediate Protection against Neutrophil-associated Lung Inflammation in Pulmonary Melioidosis.

Pulmonary melioidosis is a severe tropical infection caused by Burkholderia pseudomallei and is associated with high mortality, despite early antibiotic treatment. γδ T cells have been increasingly implicated as drivers of the host neutrophil response during bacterial pneumonia, but their role in pulmonary melioidosis is unknown. Here, we report that in patients with melioidosis, a lower peripheral blood γδ T-cell concentration is associated with higher mortality, even when adjusting for severity of illness. γδ T cells were also enriched in the lung and protected against mortality in a mouse model of pulmonary melioidosis. γδ T-cell deficiency in infected mice induced an early recruitment of neutrophils to the lung, independent of bacterial burden. Subsequently, γδ T-cell deficiency resulted in increased neutrophil-associated inflammation in the lung as well as impaired bacterial clearance. In addition, γδ T cells influenced neutrophil function and subset diversity in the lung after infection. Our results indicate that γδ T cells serve a novel protective role in the lung during severe bacterial pneumonia by regulating excessive neutrophil-associated inflammation.

Real-world study on disease burden and current clinical practice of hospital-acquired pneumonia in Japan

BackgroundHospital-acquired pneumonia (HAP) is a common nosocomial infection and is associated with high mortality. Despite advances in the understanding of the causes and prevention of HAP, it continues to be a frequent complication associated with hospital care. Presently, there are no large retrospective cohort studies on HAP in Japan. MethodsA retrospective cohort study was conducted using the Medical Data Vision Co. Ltd. database for the study period (1 April 2015 to 31 May 2018). The study population was defined based on ICD-10 codes for bacterial pneumonia, characteristics of hospitalization, and prescription of injection-only antibiotics. The study included patients ≥ 18 years of age with at least one episode of HAP during the identification period, where the episode was defined as hospitalization with HAP within the study identification period. ResultsA total of 2,968 patients were included in this study contributing to 2,979 HAP episodes. Patients with HAP were more likely to be male (64.9%) and older than age 65 (86.5%). The top three frequently prescribed antibiotics were sulbactam-ampicillin (39.7%; 1,183 episodes), tazobactam-piperacillin (28.4%; 846 episodes) and ceftriaxone (23.2%; 690 episodes). The mean (± SD) length of hospital stay during overall hospitalization and the HAP period were 49.9 (± 34.2) days and 11.3 ± 7.3 days respectively. The HAP patient mortality at discharge was 22.0%. ConclusionThe present study provided insights regarding the characteristics, treatment patterns of HAP patients in Japan. Further, the study provided noteworthy information regarding antibiotic usage trends in the aging Japanese population.

Nrf2 Regulates Inflammation by Modulating Dendritic Cell-T Cell Crosstalk during Viral-Bacterial Superinfection.

Every year millions of people are infected with influenza, which can be complicated by secondary bacterial pneumonia. One factor that may contribute to increased susceptibility to secondary bacterial infection is the modulation of inflammatory cytokines. NF erythroid 2-related factor 2 (Nrf2) has been shown to be a master regulator of the antioxidant response and various inflammatory cytokines. To test the role of Nrf2 during viral-bacterial superinfection, we used a mouse model of influenza-Staphylococcus aureus superinfection with wild-type (WT) or Nrf2-deficient (Nrf2-/-) mice. Loss of Nrf2 reduced influenza burden and increased S. aureus burden during superinfection. Additionally, Nrf2-/- mice had increased abundance of conventional type 1 dendritic cells (DCs). We then tested the interaction between DCs and T cells using an invitro model of bone marrow-derived DCs with OVA and OT-II T cells. In this system, Nrf2-/- DCs promoted a Th2/regulatory T cell response as opposed to a Th1/Th17 response by WT DCs. This was recapitulated invivo with superinfected Nrf2-/- mice having increased regulatory T cell populations. We also observed an increased median survival time of Nrf2-/- superinfected mice, due at least in part to increased IL-10 signaling, as anti-IL-10R Ab treatment reduced median survival time to levels seen in WT mice. Overall, these data suggest that loss of Nrf2 promotes differential T cell skewing mediated by DCs that promote a regulatory phenotype, increasing superinfection survival time, despite increased bacterial burden.

Evaluating omadacycline dosing regimens against drug-resistant pathogens including Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae in adults: a pharmacokinetic/pharmacodynamic analysis using Monte Carlo simulation.

The objective of this study was to evaluate the efficacy of various dosing regimens of omadacycline against main drug-resistant pathogens in the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). Monte Carlo simulations were conducted using pharmacokinetic parameters and pharmacodynamic data to calculate cumulative fractions of response (CFRs) in terms of drug area under the concentration curve/minimum inhibition concentration targets.CFR ≥ 90% was considered optimal for a dosage regimen. CFR of any approved oral/intravenous regimen with loading-dose was ≥ 90% against methicillin-resistant Staphylococcus aureus (MRSA) for ABSSSI and penicillin-resistant Streptococcus pneumonia, tetracycline-resistant Streptococcus pneumonia, MRSA and β-lactamase positive Haemophilus influenzae for CABP. In conclusion, approved oral/intravenous loading and maintenance doses of omadacycline showed enough efficacy in the treatment of ABSSI and CABP caused by the main drug-resistant pathogens.

Targeted delivery of flagellin by nebulization offers optimized respiratory immunity and defense against pneumococcal pneumonia.

Novel therapeutic strategies are urgently needed to combat pneumonia caused by Streptococcus pneumoniae strains resistant to standard-of-care antibiotics. Previous studies have shown that targeted stimulation of lung innate immune defenses through intranasal administration of the Toll-like receptor 5 agonist flagellin improves the treatment of pneumonia when combined with antibiotics. To promote translation to the clinic application, this study assessed the direct delivery of flagellin to the airways through nebulization using a vibrating mesh nebulizer in mice. Intranasal delivery achieved approximately 40% lung deposition of the administered flagellin dose, whereas nebulization yielded less than 1%. Despite these differences, nebulized flagellin induced transient activation of lung innate immunity characterized by cytokine/chemokine production and neutrophil infiltration into airways analogous to intranasal administration. Furthermore, inhalation by nebulization resulted in an accelerated resolution of systemic pro-inflammatory responses. Lastly, adjunct therapy combining nebulized flagellin and amoxicillin proved effective against antibiotic-resistant pneumococcal pneumonia in mice. We posit that flagellin aerosol therapy represents a safe and promising approach to address bacterial pneumonia within the context of antimicrobial resistance.

A Case Report on Multi Drug Resistance in Community Acquired Pneumonia Due to Escherichia coli with Cholangiocarcinoma

Escherichia coli is an important cause of severe community acquired pneumonia with mortality higher than pneumococcal pneumonia but like other gram-negative pneumonia. Antibiotics are the treatment of choice in treating pneumonia. When it comes to bacterial community-acquired pneumonia, multidrug resistant Escherichia coli (MDR E. Coli) is a less common cause than Staphylococcus aureus and Streptococcus pneumoniae. The majority of patients with community-acquired pneumonia (CAP) respond well to typical antibiotic regimens consisting of either a fluoroquinolone or a macrolide plus cephalosporin. We present a case where patient diagnosed with E. coli causing pneumonia showed MDR to various empirical antibiotics and managed with culture sensitive antibiotics. Antibiotic resistance has become a major issue for healthcare providers, where the effective management of patients will be more challenging which necessitates the need for optimising the use of antibiotics. Keywords: Multi Drug Resistance, Community Acquired Pneumonia, Escherichia Coli, Cholangiocarcinoma.

Microbial dynamics and pulmonary immune responses in COVID-19 secondary bacterial pneumonia

Secondary bacterial pneumonia (2°BP) is associated with significant morbidity following respiratory viral infection, yet remains incompletely understood. In a prospective cohort of 112 critically ill adults intubated for COVID-19, we comparatively assess longitudinal airway microbiome dynamics and the pulmonary transcriptome of patients who developed 2°BP versus controls who did not. We find that 2°BP is significantly associated with both mortality and corticosteroid treatment. The pulmonary microbiome in 2°BP is characterized by increased bacterial RNA mass and dominance of culture-confirmed pathogens, detectable days prior to 2°BP clinical diagnosis, and frequently also present in nasal swabs. Assessment of the pulmonary transcriptome reveals suppressed TNFα signaling in patients with 2°BP, and sensitivity analyses suggest this finding is mediated by corticosteroid treatment. Further, we find that increased bacterial RNA mass correlates with reduced expression of innate and adaptive immunity genes in both 2°BP patients and controls. Taken together, our findings provide fresh insights into the microbial dynamics and host immune features of COVID-19-associated 2°BP, and suggest that suppressed immune signaling, potentially mediated by corticosteroid treatment, permits expansion of opportunistic bacterial pathogens.

Antibacterial effects of Kampo products against pneumonia causative bacteria.

Community-acquired pneumonia is caused primarily by bacterial infection. For years, antibiotic treatment has been the standard of care for patients with bacterial pneumonia, although the emergence of antimicrobial-resistant strains is recognized as a global health issue. The traditional herbal medicine Kampo has a long history of clinical use and is relatively safe in treating various diseases. However, the antimicrobial effects of Kampo products against pneumonia-causative bacteria remain largely uncharacterized. In this study, we investigated the bacteriological efficacy of 11 Kampo products against bacteria commonly associated with pneumonia. Sho-saiko-To (9), Sho-seiryu-To (19), Chikujo-untan-To (91) and Shin'i-seihai-To (104) inhibited the growth of S. pneumoniae serotype 3, a highly virulent strain that causes severe pneumonia. Also, the growth of S. pneumoniae serotype 1, another highly virulent strain, was suppressed by treatment with Sho-saiko-To (9), Chikujo-untan-To (91), and Shin'i-seihai-To (104). Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against these strains ranged from 6.25-50 mg/mL and 12.5-25 mg/mL, respectively. Furthermore, Sho-saiko-To (9), Chikujo-untan-To (91), and Shin'i-seihai-To (104) suppressed the growth of antibiotic-resistant S. pneumoniae isolates. Additionally, Sho-saiko-To (9) and Shin'i-seihai-To (104) showed growth inhibition activity against Staphylococcus aureus, another causative agent for pneumonia, with MIC ranging from 6.25-12.5 mg/mL. These results suggest that some Kampo products have antimicrobial effects against S. pneumoniae and S. aureus, and that Sho-saiko-To (9) and Shin'i-seihai-To (104) are promising medicines for treating pneumonia caused by S. pneumoniae and S. aureus infection.

Whooping cough – a recurrent epidemic

Abstract Background Whooping cough (WC), or Pertussis, is a vaccine-preventable and highly contagious infectious disease. Although it has a relatively low fatality rate, approximately 13% of reported cases develop secondary bacterial pneumonia. This was because of several recurrent epidemics across Europe in the last decades, with the latest beginning in mid-2023 and still ongoing. The Central Region of Portugal is currently being affected, and this study aims to describe the current epidemic at the regional level. Methods Data from epidemiological inquiries of confirmed and probable cases of WC pertaining to the Central Region of Portugal from January 2020 till April 2024 was gathered from the mandatory report national epidemiological surveillance system (SINAVE). Both a temporal comparison of number of cases and a statistical space-time scan with permutation were conducted (software SaTScan v10.) Results A comparison by month of reported cases shows an increase in cases from September 2023 until December 2023 followed by an exponential increase from January 2024 until April 2024 denoting an ongoing epidemic. In the statistical space-time analysis of 107 reported cases between September 2023 and April 2024, 8 nonsignificant clusters were identified with different locations involved in non-overlapping periods. Conclusions The finding of several unrelated clusters, even though nonsignificant, during a short time period indicates that Pertussis transmission is ongoing at the local level probably through asymptomatic or barely symptomatic cases that act as reservoirs. Clinicians must hold a high clinical suspicion for a timely diagnosis, treatment and report and health authorities must reinforce control measures to limit the spread of this disease. Key messages • Pertussis remains a disease of significant concern recurrent outbreaks across Europe show that public health local authorities have an important role in timely management of cases and outbreaks. • Local level transmission and intervention may play a pivotal role in the epidemiologic dynamic of Pertussis.

COMPREENDENDO A INTERSEÇÃO ENTRE HIV/AIDS E PNEUMONIA: UMA ANÁLISE ABRANGENTE DA LITERATURA

INTRODUCTION: The relationship between HIV/AIDS and pneumonia is complex and multifaceted. Individuals infected with HIV have a significantly higher risk of developing pneumonia, caused by both bacterial and viral agents, due to immune suppression from the virus. OBJECTIVE: To identify in the literature the relationship between HIV/AIDS and pneumonia in the context of nursing care. MATERIALS AND METHODS: This is an integrative literature review conducted in the MEDLINE, LILACS, and BDENF databases, using the descriptors: “HIV seropositivity,” “Pneumonia,” and “nursing care.” The descriptors were combined using the boolean operator AND, covering the period from 2018 to 2024. RESULTS: The study found that HIV-positive patients tend to experience a subacute progression of Pneumocystis jirovecii pneumonia (PCP), while immunocompromised patients without HIV face rapid progression, with a higher risk of respiratory failure and mortality. CT scans showed ground-glass opacities and elevated lactate dehydrogenase levels. Non-HIV patients had longer treatment delays and higher hospitalization and mortality rates. Lymphopenia, steroid use, and pneumothorax were associated with 60-day mortality. The incidence of bacterial pneumonia in people living with HIV decreased, linked to improved CD4 counts. Children with HIV showed higher mortality from coronavirus-related pneumonia. CONCLUSIONS: Future research should expand epidemiological surveillance, explore new therapies, and investigate co-infections in at-risk groups, particularly children. Additionally, strengthening public health policies and promoting prevention education are essential to improve clinical outcomes in vulnerable populations.

Stress Can Induce Bovine Alpha-Herpesvirus 1 (BoHV-1) Reactivation from Latency

Bovine alpha-herpesvirus 1 (BoHV-1) is a significant problem for the cattle industry, in part because the virus establishes latency, and stressful stimuli increase the incidence of reactivation from latency. Sensory neurons in trigeminal ganglia and unknown cells in pharyngeal tonsils are importantsites for latency. Reactivation from latency can lead to reproductive problems in pregnant cows, virus transmission to young calves, suppression of immune responses, and bacterial pneumonia. BoHV-1 is also a significant cofactor in bovine respiratory disease (BRD). Stress, as mimicked by the synthetic corticosteroid dexamethasone, reproducibly initiates reactivation from latency. Stress-mediated activation of the glucocorticoid receptor (GR) stimulates viral replication and transactivation of viral promoters that drive the expression of infected cell protein 0 (bICP0) and bICP4. Notably, GR and Krüppel-like factor 15 (KLF15) form a feed-forward transcription loop that cooperatively transactivates immediate early transcription unit 1 (IEtu1 promoter). Two pioneer transcription factors, GR and KLF4, cooperatively transactivate the bICP0 early promoter. Pioneer transcription factors bind silent viral heterochromatin, remodel chromatin, and activate gene expression. Thus, wepredict that these novel transcription factors mediate early stages of BoHV-1 reactivation from latency.

Lefamulin dosing optimization using population pharmacokinetic and pharmacokinetic/pharmacodynamic assessment in Chinese patients with community-acquired bacterial pneumonia.

Lefamulin is the first pleuromutilin antibiotic approved for the treatment of community-acquired bacterial pneumonia (CABP). However, the pharmacokinetic/pharmacodynamic (PK/PD) characteristics in Chinese CABP patients are not fully understood. This study aimed to evaluate its microbiological efficacy against Streptococcus pneumoniae and Staphylococcus aureus via PK/PD analysis. The population PK (PopPK) model, established with foreign data was validated using data from Chinese CABP patients. PK/PD analysis was conducted for the intravenous administration of 150mg q12h for 1-h, 1.5-h and extended 2-h infusion. Oral administrations of 600mg q12h were assessed, considering original and higher plasma protein binding. Lefamulin displayed similar PK characteristics in both Chinese and Western populations. The PopPK model effectively predicted lefamulin concentrations in Chinese CABP patients. Under the dosage regimen of 150mg q12h via intravenous infusion for 1/1.5/2h, the probability of target attainments reached 98% at the minimum inhibitory concentration for both 90% S. pneumoniae and S. aureus, considering both original and higher protein binding rates. It is advisable to extend the infusion duration from 1/1.5 h-2h to minimize the risk of adverse effects at the infusion site. Regardless of fasted or fed conditions, the PTAs for 600mg q12h lefamulin via oral administration proved comparable to those for intravenous administration. This study proved that intravenous and oral administrations of lefamulin can reach preclinical PK/PD targets of S. pneumoniae and S. aureus. These findings support the optimal use of lefamulin for the safe and effective treatment of Chinese CABP patients.