Staphylococcus aureus Pneumonia in Can Tho, Vietnam: Clinical Characteristics, Antimicrobial Resistance Profile and Risk Factors of Mortality.

INTRODUCTION: Staphylococcus aureus (S. aureus) is an important pathogen in both community-acquired and hospital-acquired pneumonia. S. aureus pneumonia has a high mortality rate and serious complications. Resistance to multiple antibiotics is a major challenge in the treatment of S. aureus pneumonia. Understanding the antibiotic resistance profile of S. aureus and the risk factors for mortality can help optimize antibiotic regimens and improve patient outcomes in S. aureus pneumonia. METHODS: A prospective cohort study of 118 patients diagnosed with S. aureus pneumonia between May 2021 and June 2023 was conducted, with a 30-day follow-up period. Demographic information, comorbidities, Charlson Comorbidity Index, clinical characteristics, outcomes, and complications were collected for each enrolled case. The data were processed and analyzed using R version 3.6.2. RESULTS: S. aureus pneumonia has a 30-day mortality rate of approximately 50%, with complication rates of 22% for acute respiratory distress syndrome (ARDS), 26.3% for septic shock, and 14.4% for acute kidney injury (AKI). Among patients with methicillin-resistant S. aureus (MRSA) pneumonia treated with vancomycin (n = 40), those with a vancomycin minimum inhibitory concentration (MIC) ≤ 1 had significantly higher cumulative survival at day 30 compared to those with MIC ≥ 2 (log-rank test p = 0.04). The prevalence of MRSA among S. aureus isolates was 84.7%. Hemoptysis, methicillin resistance, acidosis (pH < 7.35), and meeting the Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) criteria for severe pneumonia were significantly associated with mortality in a multivariate Cox regression model based on the adaptive least absolute shrinkage and selection operator (LASSO). CONCLUSIONS: S. aureus pneumonia is a severe clinical condition with high mortality and complication rates. MRSA has a high prevalence in Can Tho City, Vietnam. Hemoptysis, methicillin resistance, acidosis (pH < 7.35), and meeting the IDSA/ATS criteria for severe pneumonia are risk factors for mortality in S. aureus pneumonia.

Post-COVID-19 Pulmonary Fibrosis: Facts-Challenges and Futures: A Narrative Review.

Patients with coronavirus disease 2019 (COVID-19) usually suffer from post-acute sequelae of coronavirus disease 2019 (PASC). Pulmonary fibrosis (PF) has the most significant long-term impact on patients' respiratory health, called post-COVID-19 pulmonary fibrosis (PC19-PF). PC19- PF can be caused by acute respiratory distress syndrome (ARDS) or pneumonia due to COVID-19. The risk factors of PC19-PF, such as older age, chronic comorbidities, the use of mechanical ventilation during the acute phase, and female sex, should be considered. Individuals with COVID-19 pneumonia symptoms lasting at least 12 weeks following diagnosis, including cough, dyspnea, exertional dyspnea, and poor saturation, accounted for nearly all disease occurrences. PC19-PF is characterized by persistent fibrotic tomographic sequelae associated with functional impairment throughout follow-up. Thus, clinical examination, radiology, pulmonary function tests, and pathological findings should be done to diagnose PC19-PF patients. PFT indicated persistent limitations in diffusion capacity and restrictive physiology, despite the absence of previous testing and inconsistency in the timeliness of assessments following acute illness. It has been hypothesized that PC19-PF patients may benefit from idiopathic pulmonary fibrosis treatment to prevent continued infection-related disorders, enhance the healing phase, and manage fibroproliferative processes. Immunomodulatory agents might reduce inflammation and the length of mechanical ventilation during the acute phase of COVID-19 infection, and the risk of the PC19-PF stage. Pulmonary rehabilitation, incorporating exercise training, physical education, and behavioral modifications, can improve the physical and psychological conditions of patients with PC19-PF.

The Impact of Risk Factors on Treatment Outcomes of Nosocomial Pneumonia Due to Gram-Negative Bacteria in the Intensive Care Unit.

INTRODUCTION: Nosocomial pneumonia is a common infection associated with high mortality in hospitalized patients. Nosocomial pneumonia, caused by gram-negative bacteria, often occurs in the elderly and patients with co-morbid diseases. METHODS: Original research using a prospective cross-sectional design was conducted on 281 patients in an intensive care unit setting with nosocomial pneumonia between July 2015 and July 2019. For each nosocomial pneumonia case, data regarding comorbidities, risk factors, patient characteristics, Charlson comorbidity index (CCI), Systemic Inflammatory Response Syndrome (SIRS), and quick Sepsis-Related Organ Failure Assessment (qSOFA) points and treatment outcomes were collected. Data were analyzed by SPSS 22.0. RESULTS: Nosocomial pneumonia due to gram-negative bacteria occurred in patients with neurological disorders (34.87%), heart diseases (16.37%), chronic renal failure (7.12%), and post-surgery (10.68%). Worse outcomes attributed to nosocomial pneumonia were high at 75.8%. Mechanical ventilation, change of antibiotics, and CCI ≥ 3 and qSOFA ≥ 2 were significantly negative prognostic factors (p < 0.05) on outcomes of nosocomial pneumonia. There was no difference in treatment effects between gender, age, time of onset pneumonia, SIRS score (p > 0.05). The pathogens were significant factors that influence treatment effects, but they weren't independent risk factors for poor outcomes (p = 0.823). CONCLUSIONS: Patients with nosocomial pneumonia hospitalized in intensive care units are usually associated with many underlying diseases, including neurological diseases. Mechanical ventilation, a change in antibiotics, CCI ≥ 3, and qSOFA ≥ 2 are also associated with a worse prognosis of nosocomial pneumonia. CCI and qSOFA might be used in predicting the outcome of nosocomial pneumonia.

GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed CAR T cells.

Early clinical results of chimeric antigen receptor (CAR) T cell therapy targeting B cell maturation antigen (BCMA) for multiple myeloma (MM) appear promising, but relapses associated with residual low-to-negative BCMA-expressing MM cells have been reported, necessitating identification of additional targets. The orphan G protein-coupled receptor, class C group 5 member D (GPRC5D), normally expressed only in the hair follicle, was previously identified as expressed by mRNA in marrow aspirates from patients with MM, but confirmation of protein expression remained elusive. Using quantitative immunofluorescence, we determined that GPRC5D protein is expressed on CD138+ MM cells from primary marrow samples with a distribution that was similar to, but independent of, BCMA. Panning a human B cell-derived phage display library identified seven GPRC5D-specific single-chain variable fragments (scFvs). Incorporation of these into multiple CAR formats yielded 42 different constructs, which were screened for antigen-specific and antigen-independent (tonic) signaling using a Nur77-based reporter system. Nur77 reporter screen results were confirmed in vivo using a marrow-tropic MM xenograft in mice. CAR T cells incorporating GPRC5D-targeted scFv clone 109 eradicated MM and enabled long-term survival, including in a BCMA antigen escape model. GPRC5D(109) is specific for GPRC5D and resulted in MM cell line and primary MM cytotoxicity, cytokine release, and in vivo activity comparable to anti-BCMA CAR T cells. Murine and cynomolgus cross-reactive CAR T cells did not cause alopecia or other signs of GPRC5D-mediated toxicity in these species. Thus, GPRC5D(109) CAR T cell therapy shows potential for the treatment of advanced MM irrespective of previous BCMA-targeted therapy.

Prevalence, quantification and antimicrobial resistance of Campylobacter spp. on chicken neck-skins at points of slaughter in 5 major cities located on 4 continents.

Quantitative data on Campylobacter contamination of food are lacking, notably in developing countries. We assessed Campylobacter contamination of chicken neck-skins at points of slaughter in 5 major cities in Africa (Dakar in Senegal, Yaounde in Cameroon), Oceania (Noumea in New Caledonia), the Indian Ocean (Antananarivo in Madagascar) and Asia (Ho Chi Minh City (HCMC) in Vietnam. One hundred and fifty slaughtered chickens were collected in each of the 5 major cities from semi-industrial abattoirs or markets (direct slaughter by the seller), and 65.5% (491/750) were found to be Campylobacter-positive. Two cities, Yaounde and Noumea, demonstrated high prevalence Campylobacter detection rates (92.7% and 96.7% respectively) in contrast with HCMC (15.3%). Four species were identified among 633 isolates, namely C. jejuni (48.3%), C. coli (37.3%), C. lari (11.7%) and C. upsaliensis (1%). HCMC was the only city with C. lari isolation as was Antananarivo for C. upsaliensis. C. coli was highly prevalent only in Yaounde (69.5%). Among the 491 samples positive in Campylobacter detection, 329 were also positive with the enumeration method. The number of Campylobacter colony-forming units (CFU) per gram of neck-skin in samples positive in enumeration was high (mean of the log(10): 3.2 log(10) CFU/g, arithmetic mean: 7900CFU/g). All the cities showed close enumeration means except HCMC with a 1.81 log(10) CFU/g mean for positive samples. Semi-industrial abattoir was linked to a significant lower count of Campylobacter contamination than direct slaughter by the seller (p=0.006). On 546 isolates (546/633, 86.3%) tested for antibiotic susceptibility, resistance to erythromycin, ampicillin and ciprofloxacin was observed for respectively 11%, 19% and 50%. HCMC was the city where antibiotic resistant rates were the highest (95%, p=0.014). Considering the 329 positive chickens in Campylobacter enumeration, the mean number of resistant isolates to at least 2 different antibiotic families (19.8%), may be estimated ca. 1500CFU/g; the corresponding mean of the log(10) would be 2.5 log(10)CFU/g. As chickens are sold at slaughter and brought directly at home to be cooked, these data suggest a high probability of cross-contamination. A substantial proportion of isolates are drug-resistant, which could lead to potential public health issues. Health authorities should consider measures to reduce Campylobacter contamination of chicken during farming and at slaughter, and to provide appropriate food hygiene education. Further studies are needed in particular to investigate food-handling practices in domestic kitchens.