Bacterial Pneumonia Research Articles

In Vitro Safety Study on the Use of Cold Atmospheric Plasma in the Upper Respiratory Tract.

Cold atmospheric plasma (CAP) devices generate reactive oxygen and nitrogen species, have antimicrobial and antiviral properties, but also affect the molecular and cellular mechanisms of eukaryotic cells. The aim of this study is to investigate CAP treatment in the upper respiratory tract (URT) to reduce the incidence of ventilator-associated bacterial pneumonia (especially superinfections with multi-resistant pathogens) or viral infections (e.g., COVID-19). For this purpose, the surface-microdischarge-based plasma intensive care (PIC) device was developed by terraplasma medical GmbH. This study analyzes the safety aspects using in vitro assays and molecular characterization of human oral keratinocytes (hOK), human bronchial-tracheal epithelial cells (hBTE), and human lung fibroblasts (hLF). A 5 min CAP treatment with the PIC device at the "throat" and "subglottis" positions in the URT model did not show any significant differences from the untreated control (ctrl.) and the corresponding pressurized air (PA) treatment in terms of cell morphology, viability, apoptosis, DNA damage, and migration. However, pro-inflammatory cytokines (MCP-1, IL-6, and TNFα) were induced in hBTE and hOK cells and profibrotic molecules (collagen-I, FKBP10, and αSMA) in hLF at the mRNA level. The use of CAP in the oropharynx may make an important contribution to the recovery of intensive care patients. The results indicate that a 5 min CAP treatment in the URT with the PIC device does not cause any cell damage. The extent to which immune cell activation is induced and whether it has long-term effects on the organism need to be carefully examined in follow-up studies in vivo.

High Rates of Nonsusceptibility to Common Oral Antibiotics in Streptococcus pneumoniae Clinical Isolates From the United States (2019-2021).

Streptococcus pneumoniae isolates from the United States (n = 1038; 2019-2021) were susceptible to omadacycline (99.8%), levofloxacin (99.7%), and ceftriaxone (98.1%), whereas doxycycline (80.2%), oral penicillin (63.5%), cefpodoxime (76.8%), and azithromycin (54.4%) activity was limited. Tet(M) did not affect omadacycline activity but altered activity of older tetracyclines including doxycycline, suggesting omadacycline is an important option for treatment of community-acquired bacterial pneumonia.

Outcomes of different steroid dosing regimens in critical Covid-19 pneumonia at a Kenyan hospital: A retrospective cohort study.

Among therapeutic options for severe and critical COVID- 19 infection, dexamethasone six milligrams once daily for ten days has demonstrated mortality benefit and is guideline recommended at this dose. In practice, variable doses of steroids have been used, especially in critical care settings. Our study aimed to determine the pattern of steroid dosing and outcomes in terms of critical care mortality, occurrence of dysglycaemias, and occurrence of superadded infections in patients with critical COVID-19. A retrospective cohort study was carried out on all eligible patients admitted to the Aga Khan University Hospital, Nairobi, with critical COVID-19 between 1st March 2020 and 31st December 2021. The intervention of interest was corticosteroids quantified as the average daily dose in milligrams of dexamethasone. A steroid dose of six milligrams once a day was compared to high dose steroid dosing, which was defined as any dose greater than this. The primary outcome measure was ICU mortality and secondary outcomes included occurrence of dysglycaemias, superadded infections and duration of critical care admission. The study included 288 patients. The median age was 61.2 years (IQR: 49.7, 72.5), with 71.2% of patients being male. The most common comorbidities were diabetes mellitus (60.7%), hypertension (58%), and heart disease (12.2%). The average oxygen saturation and C-reactive protein at admission were 82% [IQR: 70.0-89.0]and 113.0 [IQR: 54.0-186.0], respectively. Fifty-eight percent of patients received a standard dose (6mg) of steroids. The mortality rate was higher in the high-dose group compared to the standard-dose group; however, the difference was not statistically significant (47.9% vs 43.7% p = 0.549). The two most common steroid associated adverse effects were uncomplicated hyperglycemia (62.2%) and superimposed bacterial pneumonia (20.1%). The high-dose group had a higher incidence of uncomplicated hyperglycemia compared to the standard-dose group (63.6% vs 61.1%). However, the incidence of diabetic ketoacidosis was lower in the high dose group (0.6% vs 6.6%). Oxygen saturation at admission was associated with survival where it was lower among non-survivor patients with critical COVID-19. The study found that high-dose steroids in the treatment of critically ill patients with COVID-19 pneumonia did not confer any mortality benefit and were associated with an increased risk of dysglycemia and superimposed infections.

RNA interactome of hypervirulent Klebsiella pneumoniae reveals a small RNA inhibitor of capsular mucoviscosity and virulence

Hypervirulent Klebsiella pneumoniae (HvKP) is an emerging bacterial pathogen causing invasive infection in immune-competent humans. The hypervirulence is strongly linked to the overproduction of hypermucoviscous capsule, but the underlying regulatory mechanisms of hypermucoviscosity (HMV) have been elusive, especially at the post-transcriptional level mediated by small noncoding RNAs (sRNAs). Using a recently developed RNA interactome profiling approach iRIL-seq, we interrogate the Hfq-associated sRNA regulatory network and establish an intracellular RNA-RNA interactome in HvKP. Our data reveal numerous interactions between sRNAs and HMV-related mRNAs, and identify a plethora of sRNAs that repress or promote HMV. One of the strongest HMV repressors is ArcZ, which is activated by the catabolite regulator CRP and targets many HMV-related genes including mlaA and fbp. We discover that MlaA and its function in phospholipid transport is crucial for capsule retention and HMV, inactivation of which abolishes Klebsiella virulence in mice. ArcZ overexpression drastically reduces bacterial burden in mice and reduces HMV in multiple hypervirulent and carbapenem-resistant clinical isolates, indicating ArcZ is a potent RNA inhibitor of bacterial pneumonia with therapeutic potential. Our work unravels a novel CRP-ArcZ-MlaA regulatory circuit of HMV and provides mechanistic insights into the posttranscriptional virulence control in a superbug of global concern.

In vitro activity of delafloxacin against clinical levofloxacin-resistant Helicobacter pylori isolates.

Increasing antibiotic resistance in Helicobacter pylori necessitates research on new active molecules. In 2017, delafloxacin, a new fluoroquinolone with chemical properties of activity under acidic conditions, was approved for treatment of community-acquired bacterial pneumonia and acute bacterial skin and soft-tissue infections. Mutations in gyrA are responsible for fluoroquinolone resistance, but certain clinical isolates of H. pylori appear to display a dual phenotype: resistance to levofloxacin associated with very low delafloxacin MICs. To estimate epidemiological cut-off (ECOFF) values and to identify mutations in the gyrA gene, specific to FQ resistance, without increasing the MICs of delafloxacin. Clinical strains (n = 231) were collected in the bacteriology laboratory of Poitiers University Hospital over a 2 year period to determine the ECOFF of delafloxacin. Retrospectively, 101 clinical strains with an levofloxacin-resistant phenotype (MIC > 1 mg/L) were selected from 2018 to 2022 for delafloxacin MIC determination and QRDR (gyrA) sequencing. The estimated ECOFF of delafloxacin was ≤0.125 mg/L. No H. pylori isolate showed a levofloxacin-sensitive phenotype with a delafloxacin MIC of >0.125 mg/L. Among the levofloxacin-resistant H. pylori isolates, 53.5% had delafloxacin MICs of ≤0.125 mg/L. The N87I mutation was associated with dual levofloxacin/delafloxacin resistance (P < 0.001) in contrast to the N87K and D91N mutations (P > 0.05). Mutations D91G and D91Y were not associated with a delafloxacin resistance phenotype (P > 0.05). Delafloxacin seems to be a therapeutic alternative for levofloxacin-resistant strains with greater in vitro activity. However, further clinical/biological investigations are required to determine its efficacy in H. pylori eradication.

Immune status of patients with community-acquired pneumonia associated with a new coronavirus infection and other viral and bacterial pathogens

Despite the fact that the state of the individual’s immune system plays an important role in developing community-acquired pneumonia, its clinical features are determined not only by immune response characteristics, but also by the nature of the infectious agent. The aim of the work was to assess immune status of patients with community-acquired pneumonia with lung damage ranging from 2 to 12%, in whom pathogens of a viral, bacterial and fungal nature were verified (n = 96, aged 46,3±20,5) who were admitted to the hospital 5–7 days after disease onset. Materials and methods. The selection of smears and sputum specimens was carried out on day 1 after admission. COVID-19 pathogen was analyzed in smears by PCR using the Vector-PCRR-2019-nCoV-RG kit (SSC Vector of Rospotrebnadzor, Russia). Biochemical activity, colony morphology, and pathogen concentration (in the amount of ≥ 105 CFU/ml) were also evaluated. Based on the results of preliminary studies, target patients groups were formed: with a new coronavirus infection caused by the SARS-CoV-2 gene variant B.1.1.529 (Omicron) (n = 33); with COVID-19 and bacterial pathogens (n = 17); with COVID-19 and combined bacterial and fungal infection (n = 16); patients with identified pathogens of bacterial infections (n = 13); patients with combined bacterial and fungal infection (n = 17). The relative and absolute level of CD45+CD3+ lymphocytes, CD45+CD3+CD4+ cells, CD45+CD3+CD8+ lymphocytes, CD45+CD3-CD16+CD56+ cells, CD45+CD3+CD16+CD56+ lymphocytes, CD45+CD45RO–CD45RA+ and CD45+CD45RO+CD45RA– lymphocytes, CD45+CD19+ cells, CD45+CD5+CD19–CD27– and CD45+CD19+CD5–CD27– lymphocytes, CD45+CD19+CD5–CD27+ cells was assessed in all volunteers. Results. The analysis of the immune status of patients with community-acquired pneumonia associated with Omicron gene variant new coronavirus infection revealed T-lymphocytopenia, a decreased number of CD8+ lymphocytes, an increased relative and absolute number of NK cells. In COVID-19 patients, who also had bacterial pathogens verified, there was a decrease in relative and absolute number of T-helper cells, an increased relative and absolute number of B and B2 lymphocytes. In COVID-19-negative volunteers with bacterial and bacterial-fungal community-acquired pneumonia, the relative and absolute level of B and B2 lymphocytes, as well as the general memory B cell population, was increased. In contrast to COVID-19-positive patients, in the absence of T-lymphocytopenia, a decreased number of CD4+ cells and rise in number of cytotoxic lymphocytes were recorded in patients of these groups. Conclusions. The data obtained indicate that in the immune status of patients with community-acquired pneumonia, depending on the nature of the infectious agent, changes in relative and absolute level of T-helper cells, cytotoxic lymphocytes, as well as in the qualitative and quantitative B-lymphocyte population composition are recorded.

Simultaneous distinct cutaneous fungal infections with chromoblastomycosis due to Exophiala xenobiotica and hyalohyphomycosis due to Scedosporium apiospermum in a patient with severe cellular immunodeficiency.

Deep-seated dermatomycosis is a rare disease that is often caused by trauma and/or systemic immunodeficiency. We describe a case of chromoblastomycosis complicated by hyalohyphomycosis that occurred simultaneously at different sites. A 92-year-old Japanese man who had been taking oral prednisolone for an IgG4-related respiratory disease visited our clinic. He developed brownish plaques with grayish-white scales with pseudo-carcinomatous hyperplasia and numerous brownish muriform cells developing in the dermis of his right hand, and multiple painful abscesses with pustules and papules and numerous hyphae within and around the histiocytes in the dermis of his right lower leg. Upon skin tissue culture and DNA sequencing, Exophiala xenobiotica and Scedosporium apiospermum were detected separately. He had severe cellular immunodeficiency indicated by low levels in the phytohemagglutinin (PHA)-stimulated lymphocyte transformation test (LTT) and serum interferon-gamma (IFN-γ), although his humoral immunity was normal. The patient died of bacterial pneumonia, despite antifungal drug treatment for 2 months. IFN-γ producing type 1 T helper (Th1) cells play an important role in the defense against fungal infections, however, corticosteroids specifically suppress Th1 cell responses and promote the induction of fungal infection. Measurement of PHA-stimulated LTT and serum IFN-γ may be useful in determining the severity and prognosis of deep-seated dermatomycosis in patients undergoing corticosteroid treatment.

Outcome of intravenous and inhaled polymyxin B treatment in patients with multidrug-resistant gram-negative bacterial pneumonia

PurposeThe incidence of pneumonia caused by multidrug-resistant gram-negative bacteria (MDR GNB) is increasing, which imposes significant burden on public health. Inhalation combined with intravenous polymyxins has emerged as a viable treatment option. However, pharmacokinetic studies focusing on intravenous and inhaled polymyxin B (PMB) are limited. MethodsThis study included seven patients with MDR GNB-induced pneumonia who were treated with intravenous plus inhaled PMB from March 1 to November 30, 2022, in the intensive care unit of the First Affiliated Hospital of Zhejiang University School of Medicine. Clinical outcomes and therapeutic drug monitoring data of PMB in both plasma and epithelial lining fluid (ELF) were retrospectively reviewed. ResultsMedian PMB concentrations in the ELF were 7.83 (0.72–66.5), 116.72 (17.37–571.26), 41.1 (3.69–133.78) and 33.82 (0.83–126.68) mg/L at 0, 2, 6 and 12 h, respectively, and were much higher than those detected in the serum. ELF concentrations of PMB at 0, 2, 6 and 12 h were higher than the minimum inhibitory concentrations of pathogens isolated from the patients. Steady-state concentrations of PMB in the plasma were >2 mg/L in most patients. Of the patients, 57.14% were cured and 71.43% showed a favourable microbiological response. The incidence of side effects with PMB was low. ConclusionsInhaled plus intravenous PMB can achieve high ELF concentrations and favourable clinical outcomes without an increased adverse effect profile. This treatment approach appears promising for the treatment of patients with pneumonia caused by MDR-GNB.

Clinical and Microbiological Characteristics of Febrile Neutropenia During Induction Chemotherapy in Adults With Acute Leukemia.

Few studies regarding infectious causes of febrile neutropenia (FN) in Mexico are available. We aimed to describe clinical and microbiological characteristics of FN episodes during induction chemotherapy in adults with acute leukemia. This retrospective cohort from a Mexican tertiary care center included adults with newly diagnosed acute leukemia between January 2014, and December 2018. Clinical and microbiological characteristics were summarized using descriptive statistics. Univariate analyses for associations between clinical characteristics and FN and/or death were made; logistic regression analysis was performed to assess relationships with FN. Kaplan-Meier survival estimates were modeled for antimicrobial prophylaxis and FN. Ninety-five patients were included. Median age was 28 (IQR 20-43), 49 (52%) were males, and 74 (78%) developed FN (74/95). Among these, 98% had an identified source of infection (73/74) and 65% had >1. Common infections were urinary tract infection (24%), bacterial sinusitis (20%), and bacterial pneumonia (19%). Gram-negatives were the most frequently isolated microorganisms (69%), followed by Gram-positives (21%), and fungi (9%). Antimicrobial prophylaxis was inversely associated with FN (aOR = 0.07, CI 0.008-0.060, p = 0.02). Invasive fungal diseases were associated with 30-day mortality (aOR = 9.46, 95% CI 1.66-54.05). Infections caused 98% of the FN episodes. Gram-negative bacteria are the most common pathogens.

Predictive signature of murine and human host response to typical and atypical pneumonia

BackgroundPneumonia due to typical bacterial, atypical bacterial and viral pathogens can be difficult to clinically differentiate. Host response-based diagnostics are emerging as a complementary diagnostic strategy to pathogen detection.MethodsWe used...

Point-of-Care Ultrasound for Earlier Detection of Pediatric Pneumonia.

An 8-month-old infant presented to a general emergency department with chief complaints of rhinorrhea, decreased activity, and fever. A point-of-care lung ultrasound (LUS) was performed at bedside with potential early findings of pneumonia. Based on these findings on LUS, a chest radiograph (CXR) was ordered and performed with no acute findings. He was discharged without antibiotics based on these findings; unfortunately, he returned two days later with worsening symptoms requiring chest tube placement, mechanical ventilation, and prolonged hospitalization for complicated bacterial pneumonia. Pneumonia is a major cause of pediatric morbidity and mortality worldwide. Despite evidence supporting the utilization of LUS for the diagnosis of pediatric pneumonia, CXR remains the default imaging for clinical decision-making in most settings. In this case, earlier antibiotics and higher reliance on LUS for clinical decision-making may have prevented the morbidity associated with this hospitalization.

An in-depth review of pneumonia and the combination therapy of pneumonia with Levofloxacin and Cefixime

Pneumonia is one of the most common diseases in the world. When we go to the hospital, we can see and hear many patients suffering from pneumonia. A large number of people die from pneumonia every year all over the world. With the development of medical industry and the occurrence and invention of many drugs, pneumonia can be dealt with by using the drugs to kill the pathogens. However, how to use a more effective and economic-friendly approach to deal with pneumonia is still worth discussing. Now, there is a more effective way-combining two kinds of antibiotics to deal with pneumonia. In this essay, I will give an introduction of pneumonia, including its history, its symptoms, its impact, etc. One of the main pathogenic bacteria of pneumonia, Streptococcus pneumoniae, will also be discussed. Two approaches with some important disadvantages that people use to deal with pneumonia will be briefly discussed. Then, I will elaborate Levofloxacin and Cefixime, and how people combine Levofloxacin and Cefixime to deal with pneumonia.

Typical pneumonia among human immunodeficiency virus-infected patients in public hospitals in southern Ethiopia.

Typical pneumonia is a pressing issue in the treatment of human immunodeficiency virus (HIV) patients, especially in Sub-Saharan Africa, where it remains a significant menace. Addressing this problem is crucial in improving health outcomes and the reduction of the burden of diseases in this vulnerable category of patients. To determine the prevalence of community-acquired typical pneumonia among HIV patients in Public Hospitals in southern Ethiopia. A cross-sectional study was done among 386 HIV patients clinically suspected of typical pneumonia attending the anti-retroviral therapy (ART) clinics of two hospitals from March to September 2022. A pretested structured questionnaire was employed to collect the demographic, clinical, and behavioral data. Sputum samples were collected and inspected for bacteria following standard procedures, and antimicrobial susceptibility testing was performed employing the Kirby-Bauer disk diffusion method. Besides, extended-spectrum β-lactamase (ESβL) and carbapenemase-producing Gram-negative bacteria were inspected by the double disk synergy test and modified carbapenem inactivation method. Descriptive and inferential statistical analyses were also done. Overall, 39.1% (151/386) of sputum cultures (95% Confidence Interval: 32.4-44) were bacteriologically positive. A total of 151 bacteria were identified, comprising 72.8% (n = 110) of Gram-negative bacteria. The predominant isolate was Klebsiella pneumoniae (25.8%, n = 39), followed by Staphylococcus aureus (17.9%, n = 27); 59.6% (n = 90) of the entire isolates were multidrug-resistant (MDR). Forty percent (11/27) of S. aureus were methicillin-resistant S. aureus (MRSA), and 28.1% (n = 31) and 20.9% (n = 23) of Gram-negative bacteria were extended-spectrum beta-lactamases (ESBL) and carbapenemase producers, respectively. Occupational status, alcohol consumption, cluster of differentiation4 (CD4) Thymocyte cell count < 350, interruption of trimethoprim-sulfamethoxazole prophylaxis and antiretroviral treatment, and recent viral load ≥ 150 were found statistically significant. The higher rates of MDR, MRSA, ESBL, and carbapenem-resistant Enterobacterales (CRE) indicate that bacterial pneumonia is a vexing problem among HIV patients and therefore it is advisable to implement an antimicrobial stewardship program in the study area.

Bacterial stroke-associated pneumonia: microbiological analysis and mortality outcome

BackgroundStroke-associated pneumonia (SAP) considerably burden healthcare systems. This study aimed to identify predictors of developing SAP in acute ischemic stroke patients admitted to the Stroke Unit at Manial Specialized Hospital factors with microbiological causality and impact on 30-day mortality.MethodsThis was a retrospective cohort study. All patients with acute ischemic stroke admitted to the Stroke Unit at Manial Specialized Hospital (from February 2021 to August 2023) were divided into the SAP and non-SAP groups. Detailed clinical characteristics and microbiological results were recorded.ResultsFive hundred twenty-two patients diagnosed with acute ischemic stroke (mean age of 55 ± 10) were included. One hundred sixty-nine (32.4%) of stroke patients developed SAP; Klebsiella pneumoniae was the most commonly detected pathogen (40.2%), followed by Pseudomonas aeruginosa (20.7%). Bacteremia was identified in nine cases (5.3%). The number of deaths was 11, all of whom were diagnosed with SAP, whereas none from the non-SAP group died (P < 0.001). The binary logistic regression model identified three independent predictors of the occurrence of SAP: previous history of TIA/stroke (OR = 3.014, 95%CI = 1.281–7.092), mechanical ventilation (OR = 4.883, 95%CI = 1.544–15.436), and bulbar dysfunction (OR = 200.460, 95%CI = 80.831-497.143).ConclusionsStroke-associated pneumonia was reported in one-third of patients with acute ischemic stroke, adversely affecting mortality outcomes. Findings showed that the main predictors of SAP were bulbar dysfunction, the use of mechanical ventilation and previous history of TIA/stroke. More attention to these vulnerable patients is necessary to reduce mortality.

Testing for Blastomycosis, Coccidioidomycosis, and Histoplasmosis at a Major Commercial Laboratory, United States, 2019-2024.

Blastomycosis, coccidioidomycosis, and histoplasmosis are environmentally acquired fungal diseases that clinically resemble bacterial and viral community-acquired pneumonia and require laboratory testing for diagnosis. Patients frequently present to primary care and experience diagnostic delays when a fungal etiology is not initially suspected. Current national-level public health surveillance for these diseases is limited and does not include laboratory data, so nationwide testing practices are unknown. We identified laboratory tests for blastomycosis, coccidioidomycosis, and histoplasmosis ordered during 1 March 2019-29 February 2024 and performed within a major national commercial laboratory system. We analyzed test results, patient and healthcare provider features, reasons for testing, and temporal trends. Results included 5693 Blastomyces complement fixation tests (of those, 12% were positive), 71 858 immunodiffusion tests (0.1% positive), and 1186 serum enzyme immunoassay (EIA) tests (11% positive); 154 989 Coccidioides EIA immunoglobulin M results (5% positive) and 154 968 immunoglobulin G results (8% positive); and 46 346 Histoplasma complement fixation tests (30% positive), 49 062 immunodiffusion tests (1% positive), 35 506 serum EIA tests (4% positive), and 82 489 urine EIA tests (2% positive). Most histoplasmosis (58%-74%) and blastomycosis (42%-68%) tests were ordered from hospitals, whereas coccidioidomycosis tests were most frequently ordered by primary care providers (40%). A yearly average of 2727 positive tests were ordered by healthcare providers in states without public health surveillance for these diseases. Blastomycosis, coccidioidomycosis, and histoplasmosis are likely underdetected in primary care settings or by public health surveillance. Increased testing by primary care providers and expanded surveillance are needed to reduce disease burden.

Bacterial Pneumonia And Its Association With Chronic Periodontal Disease Among The Patients Attending At Barind Medical College Hospital, Rajshahi

Bacterial Pneumonia And Its Association With Chronic Periodontal Disease Among The Patients Attending At Barind Medical College Hospital, Rajshahi

Prevalence and patterns of multidrug-resistant bacteria isolated from sputum samples of patients with bacterial pneumonia at a tertiary hospital in Tanzania

BackgroundAntimicrobial resistance affects the treatment of several bacterial infections, including pneumonia. This subsequently increased the morbidity and mortality rates of patients with bacterial pneumonia, especially in resource-limited settings. In this study, we aimed to determine the patterns of multidrug-resistant (MDR) bacteria isolated from the sputum samples of patients with bacterial pneumonia attending a tertiary hospital in Tanzania.MethodologyA retrospective cross-sectional study was conducted. It involved reviewing the laboratory sputum data in the laboratory information system at Muhimbili National Hospital in Tanzania. The sputum samples were previously processed using standard methods (culture, Gram staining, and biochemical tests) to isolate and identify the bacteria. At the same time, antibiogram profiles were determined using antimicrobial susceptibility tests. Bacterial isolates that expressed MDR patterns were identified. Demographic information was collected from patients' medical records. We used the chi-square test to determine factors associated with MDR. A p-value < 0.05 was considered significant.ResultsWe retrieved and analysed 169 laboratory records of patients with a provisional clinical diagnosis of bacterial pneumonia confirmed in the microbiology laboratory. Nearly 98% of the records were from adult patients. The patients’ mean age was 48.3 years and 17.3 standard deviations. About 84% of the isolated bacteria were Gram-negative; the most predominant was Klebsiella pneumoniae (59/142; 41.5%). The predominant Gram-positive bacteria was Staphylococcus aureus (25/27; 92.6%). Furthermore, 80 out of 169 (47.3%) bacteria were MDR; Klebsiella pneumoniae (32.5%) was predominant. In addition, 50% of Staphylococcus aureus was methicillin resistance. MDR bacterial pneumonia was highly observed in patients admitted to the Intensive Care Unit (p < 0.05).ConclusionsAlthough our study was limited by variations in the number of bacterial isolates subjected to the same antibiotic drugs and a lack of information on risk factors such as occupation, smoking history, and marital status, we observed that a high proportion of bacterial pneumonia is caused by MDR Gram-negative bacteria in our local setting. These results inform the need to improve infection prevention control measures in hospitals to reduce the burden of MDR bacteria in our settings and other similar resource-limited settings.

Extracorporeal life support use in patients with bronchopulmonary dysplasia: A single center case series.

Preterm pediatric patients with bronchopulmonary dysplasia (BPD) represent a subgroup previously deemed high risk candidates for ECLS (extracorporeal life support) due to suspected high mortality or increased post ECLS morbidity. The aim of this study was to determine outcomes for patients with an established history of BPD who subsequently required ECLS. A single center retrospective review was performed between 01/2010-06/2022 for patients less than 2years of age, born prematurely (<32weeks) with a subsequent diagnosis of BPD, and who required ECLS for respiratory failure. Demographic and clinical data, including ECLS data, were collected. Speech, language, feeding/swallowing, cognitive, hearing, vision, or motor function deficits were obtained with a median follow up of 42months following discharge. Nineteen patients met criteria. The median birth weight and gestational age was 0.86kg (IQR 0.73, 1.0) and 26weeks (IQR 25, 27), respectively. The median chronological age at cannulation was 12.1months. The most common etiologies for respiratory failure requiring ECLS were viral (68.4%) and bacterial (21.1%) pneumonia. Survival to decannulation was 78.9% (15/19) and survival to hospital discharge was 63.2% (12/19). Amongst survivors to discharge, 42% (5/12) required new or additional home oxygen and 50% (6/12) were noted to have neurodevelopmental/behavioral concerns on follow up at 1year with 25% (3/12) with concerns beyond a year. Patients with underlying BPD who require ECLS have comparable mortality and long-term neurodevelopmental outcomes to non-BPD patients with respiratory failure. This information can be useful when considering ECLS candidacy and providing family counseling.

Nafithromycin (MIQNAF®): ultramodern lactone ketolide designed to treat community acquired bacterial pneumonia (CABP)

Nafithromycin (MIQNAF®): ultramodern lactone ketolide designed to treat community acquired bacterial pneumonia (CABP)

Targeted degradation of extracellular mitochondrial aspartyl-tRNA synthetase modulates immune responses

The severity of bacterial pneumonia can be worsened by impaired innate immunity resulting in ineffective pathogen clearance. We describe a mitochondrial protein, aspartyl-tRNA synthetase (DARS2), which is released in circulation during bacterial pneumonia in humans and displays intrinsic innate immune properties and cellular repair properties. DARS2 interacts with a bacterial-induced ubiquitin E3 ligase subunit, FBXO24, which targets the synthetase for ubiquitylation and degradation, a process that is inhibited by DARS2 acetylation. During experimental pneumonia, Fbxo24 knockout mice exhibit elevated DARS2 levels with an increase in pulmonary cellular and cytokine levels. In silico modeling identified an FBXO24 inhibitory compound with immunostimulatory properties which extended DARS2 lifespan in cells. Here, we show a unique biological role for an extracellular, mitochondrially derived enzyme and its molecular control by the ubiquitin apparatus, which may serve as a mechanistic platform to enhance protective host immunity through small molecule discovery.