Pseudomonas Infection Research Articles

Human airway epithelium controls Pseudomonas aeruginosa infection via inducible nitric oxide synthase.

Airway epithelial cells play a central role in the innate immune response to invading bacteria, yet adequate human infection models are lacking. We utilized mucociliary-differentiated human airway organoids with direct access to the apical side of epithelial cells to model the initial phase of Pseudomonas aeruginosa respiratory tract infection. Immunofluorescence of infected organoids revealed that Pseudomonas aeruginosa invades the epithelial barrier and subsequently proliferates within the epithelial space. RNA sequencing analysis demonstrated that Pseudomonas infection stimulated innate antimicrobial immune responses, but specifically enhanced the expression of genes of the nitric oxide metabolic pathway. We demonstrated that activation of inducible nitric oxide synthase (iNOS) in airway organoids exposed bacteria to nitrosative stress, effectively inhibiting intra-epithelial pathogen proliferation. Pharmacological inhibition of iNOS resulted in expansion of bacterial proliferation whereas a NO producing drug reduced bacterial numbers. iNOS expression was mainly localized to ciliated epithelial cells of infected airway organoids, which was confirmed in primary human lung tissue during Pseudomonas pneumonia. Our findings highlight the critical role of epithelial-derived iNOS in host defence against Pseudomonas aeruginosa infection. Furthermore, we describe a human tissue model that accurately mimics the airway epithelium, providing a valuable framework for systemically studying host-pathogen interactions in respiratory infections.

Obstetrical Outcomes in Women With a History of Bladder Augmentation.

To evaluate possible problems during pregnancy or delivery in women with pediatric bladder augmentation. Eleven of 59 women, who had undergone bladder augmentation in our pediatric hospital during 1990-2019, had given birth in our hospital district afterwards and their obstetrical records were evaluated. Median age at first delivery was 32 years (range 26-42). Six patients had myelomeningocele, two had bladder exstrophy and the remainder had VATER association, epispadias or traumatic paraplegia with vesicovaginal fistula. The patients had altogether 18 children (all singletons). Catheterizations were performed through continent stoma in six cases and through urethra in five cases. None of the patients needed an indwelling catheter before delivery. Antibiotic prophylaxis was initially in use during two pregnancies. Symptomatic urinary tract infections (UTIs) developed for five mothers in 11 pregnancies without prophylaxis and prophylaxis was continued after UTI in these cases. Three of the five mothers with UTI were treated with intravenous antibiotics due to pseudomonas infection (three infections) or pyelonephritis (one).Two patients with myelomeningocele delivered vaginally (one woman three times and one woman once). In the remaining 14 cases a cesarean section (CS) was performed (two urgent and one emergency CS). A urologist was present in seven CSs. Some difficulties accessing the uterus were reported in seven surgeries. There were 10-term, three late-preterm and one very preterm delivery. In four cases the information on gestational age was unavailable. Six newborns had respiratory problems, two had severe asphyxia. One newborn had myelomeningocele like her mother. Risk for UTIs during pregnancy is high in bladder augmentation patients, hence prophylactic antibiotics are justified. A multidisciplinary team should be involved in the planning of delivery. When indicated for obstetrical or urological reasons, an elective cesarean section with a urologist present may be the most rational option for many, although vaginal delivery is possible in selected patients.

Impact of Antimicrobial Therapy on Mortality and Readmission in Multidrug-Resistant Pseudomonas Infections: A Retrospective Study at Dammam Medical Complex

Impact of Antimicrobial Therapy on Mortality and Readmission in Multidrug-Resistant Pseudomonas Infections: A Retrospective Study at Dammam Medical Complex

The emerging role of photodynamic therapy in the treatment of cutaneous infections.

Cutaneous infections pose ongoing challenges to standard treatments due to resistance and limited efficacy. Photodynamic therapy (PDT) emerges as a promising supplement or an alternative to address complicated cases. In this review, we comprehensively review PDT's safety and efficacy in treating cutaneous infections. A PubMed systematic review with search terms for PDT treatment, hair, skin, and nail infections. There were a total of 43 studies on the use of PDT in cutaneous infections which discussed the treatment of viral (N.=20), bacterial (N.=11), fungal (N.=9), and protozoal (N.=3) infections. There is evidence for using PDT, mostly 5-aminolevulinic acid (5-ALA) and methyl aminolevulinate (MAL), in the treatment of cutaneous infections. Most evidence for viral infections involved treatment with 5-ALA PDT in condyloma acuminatum (CoAc), verruca vulgaris, and molluscum contagiosum. In bacterial infections, 5-ALA and MB PDT have been used to achieve complete remission in refractory Pseudomonas and atypical mycobacteria infections without recurrence. In onychomycosis, MAL PDT achieved a 40.9% cure rate and MB PDT showed a 77.8-100% cure rate with no reports of recurrence. Parasitic infections, such as leishmaniasis have also been successfully treated with both 5-ALA and MAL PDT. PDT is a promising treatment option for cutaneous infections, with growing evidence for its utility in treating cutaneous bacterial, viral, fungal, and parasitic infections, particularly those that fail standard treatments. Side effects were mostly limited to localized pain with good outcomes and low recurrence rates.

Therapeutic Interventions for Pseudomonas Infections in Cystic Fibrosis Patients: A Review of Phase IV Trials.

Pseudomonas aeruginosa (Pa) poses a significant threat to individuals with cystic fibrosis (CF), as this bacterium is highly adaptable and resistant to antibiotics. While early-stage Pa infections can often be eradicated with aggressive antibiotic therapy, chronic infections are nearly impossible to eliminate and require treatments that focus on long-term bacterial suppression. Without such suppression, these persistent infections can severely damage the lungs, leading to serious complications and a reduced life expectancy for CF patients. Evidence for a specific treatment regimen for managing Pa infections in CF patients remains limited. This narrative review provides a detailed analysis of antimicrobial therapies assessed in completed phase IV trials, focusing on their safety and efficacy, especially with prolonged use. Key antibiotics, including tobramycin, colistin, meropenem, aztreonam, ceftolozane/tazobactam, ciprofloxacin, and azithromycin, are discussed, emphasizing their use, side effects, and delivery methods. Inhaled antibiotics are preferred for their targeted action and minimal side effects, while systemic antibiotics offer potency but carry risks like nephrotoxicity. The review also explores emerging treatments, such as phage therapy and antibiofilm agents, which show promise in managing chronic infections. Nonetheless, further research is necessary to enhance the safety and effectiveness of existing therapies while investigating new approaches for better long-term outcomes.

Genetic profiling of virulence genes among Pseudomonas Aeruginosa isolates recovered from diseased chickens

Pseudomonas aeruginosa (P. aeruginosa) is regarded as an opportunistic organism for bird species. Also is one can be mentioned as an example of an environment-associated infection that results in severe disease in poultry farms, Indeed, we detected the incidence of P. aeruginosa in chickens and also discovered the implicated virulence genes and antibiotic-resistant mechanism. Two hundred cases were collected from broiler and layer chicken organs (heart blood, heart, and lungs) that suffered from some respiratory manifestation and septicemia in addition to yolk sacs from one-day-old chicks, which were examined bacteriologically and Serologically. The studied isolates were tested against eight antimicrobial discs. Bacterial DNA was analyzed using polymerase chain reaction (PCR) against six virulence genes (lasL, lasB toxA, exoU, exoT, and oprl genes). Eighteen isolates out of 200 (9%) of P. aeruginosa were defined. Serologically the isolates were related to more serogroup (O1,O4,O6, O11 and O12) P. aeruginosa. PCR defined the existence of P. aeruginosa by detection of the 16SRNA gene. All isolates showed 100% multidrug resistance (MDR) to more than one antimicrobial disc (sulfamethoxazole, erythromycin, tetracycline, and ampicillin). Conversely, those isolates exhibited 100% sensitivity to ciprofloxacin, and four of them showed sensitivity to norfloxacin with a percentage of (22.2%). In addition to 15 isolates showed resistance of 83.3% percent to streptomycin and nalidixic acid. By PCR test, all examined P. aeruginosa strains carried four virulence genes (lasI, toxA, exoU, and oprl). However, only three strains carried lasB, and four carried the exoT gene. In conclusion, we confirmed the presence of different factors of virulence for P. aeruginosa and MDR to more than one antimicrobial drug. So, restricting Pseudomonas infection in poultry requires strict biosecurity measures to control and eradicate the infection by P. aeruginosa

Impact of TAS2R38 polymorphisms on nasal nitric oxide and Pseudomonas infections in primary ciliary dyskinesia: relation to genotype

ObjectivePrimary ciliary dyskinesia (PCD) severity has been related to genotype and levels of nasal nitric oxide (nNO). The most common TAS2R38 haplotypes (PAV/PAV, PAV/AVI, AVI/AVI) encoding the bitter taste receptor...

Extracellular vesicles released by host epithelial cells during Pseudomonas aeruginosa infection function as homing beacons for neutrophils

BackgroundPseudomonas aeruginosa (PA) is an opportunistic pathogen that can cause sight threatening infections in the eye and fatal infections in the cystic fibrosis airway. Extracellular vesicles (EVs) are released by host cells during infection and by the bacteria themselves; however, there are no studies on the composition and functional role of host-derived EVs during PA infection of the eye or lung. Here we investigated the composition and capacity of EVs released by PA infected epithelial cells to modulate innate immune responses in host cells.MethodsHuman telomerase immortalized corneal epithelial cells (hTCEpi) cells and human telomerase immortalized bronchial epithelial cells (HBECs) were treated with a standard invasive test strain of Pseudomonas aeruginosa, PAO1, for 6 h. Host derived EVs were isolated by qEV size exclusion chromatography. EV proteomic profiles during infection were compared using mass spectrometry and functional studies were carried out using hTCEpi cells, HBECs, differentiated neutrophil-like HL-60 cells, and primary human neutrophils isolated from peripheral blood.ResultsEVs released from PA infected corneal epithelial cells increased pro-inflammatory cytokine production in naïve corneal epithelial cells and induced neutrophil chemotaxis independent of cytokine production. The EVs released from PA infected bronchial epithelial cells were also chemotactic although they failed to induce cytokine secretion from naïve HBECs. At the proteomic level, EVs derived from PA infected corneal epithelial cells exhibited lower complexity compared to bronchial epithelial cells, with the latter having reduced protein expression compared to the non-infected control.ConclusionsThis is the first study to comprehensively profile EVs released by corneal and bronchial epithelial cells during Pseudomonas infection. Together, these findings show that EVs released by PA infected corneal and bronchial epithelial cells function as potent mediators of neutrophil migration, contributing to the exuberant neutrophil response that occurs during infection in these tissues.

P210 Isolation frequency and abundance of Pseudomonas aeruginosa (Pa) in people with CF with chronic pseudomonas infection decreases following initiation of elexacaftor/tezacaftor/ivacaftor (ETI)

P210 Isolation frequency and abundance of Pseudomonas aeruginosa (Pa) in people with CF with chronic pseudomonas infection decreases following initiation of elexacaftor/tezacaftor/ivacaftor (ETI)

Botanical Control of Multiple Drug Resistant Pseudomonas aeruginosa infection in Clarias gariepinus

Pseudomonas aeruginosa is a Gram-negative, rod-shaped bacterium which can cause opportunistic infections in fishes. Ethanolic leaf extract of Moringa oleifera was used in the treatment of Pseudomonas aeruginosa infected Clarias gariepinus for a period of 10 days. Pathogen-free Clarias gariepinus fingerlings (n=120) were randomly distributed into four different groups (A-D). Group A, Infected Clarias gariepinus without treatment; group B, Infected Clarias gariepinus treated with ciprofloxacin 250 mg/mL); group C, Infected Clarias gariepinus treated with 500 mg/L Moringa oleifera extract; and group D, Infected Clarias gariepinus treated with 1500 mg/L Moringa oleifera extract. A 0.1 mL aliquot of 7.2×105 CFU/mL of Pseudomonas aeruginosa culture was intra-peritoneally injected into the body of the fingerlings to induce infection. The gill of fish was excised, homogenized and centrifuged to ascertain oxidative stress, while histological examination followed thereafter. The minimum inhibitory concentration of the ethanol extract was 125 mg/mL while the minimum bactericidal concentration was at 500 mg/mL. Gross morphology examination showed hemorrhage in the gill and mouth, and swollen abdomen, after 72 h of infection. The weight of Pseudomonas aeruginosa infected Clarias gariepinus before and after treatment showed no significant differences (P > 0.05) among the groups. There was significant (p<0.05) reduction in oxidative stress parameters examined. Histopathological changes noticed were minor hemorrhage epitheliocystis and damaged gill lamella. Total bacterial count showed a reduction in the Pseudomonas load in groups C and D over the period of study thus, indicating strong potentials of Moringa oleifera in the control of fish Pseudomonas infection.

Prevalence of Antibiotic Use in Hospitalized COVID-19 Patients: An Observational Study in Secondary Healthcare Hospitals in Kosovo

INTRODUCTION: Globally, the high use of antibiotics among hospitalized patients diagnosed with COVID-19 has been reported despite evidence that bacterial coinfections are uncommon. This issue raised our concerns, as there was a report on high frequency of antibiotic resistant bacterial infections in COVID-19 patients admitted to the intensive care unit. Thus, we conducted a study to determine the prevalence of antibiotic use for hospitalized acute COVID-19 infection in secondary healthcare hospitals in Kosovo. MATERIALS AND METHODS: A cross sectional study was conducted among patients with acute COVID-19 admitted to secondary healthcare hospitals in Kosovo. A modified Infectious Diseases International Research Initiative (ID-IRI) questionnaire was used to collect information in 460 COVID-19 PCR positive patients. RESULTS: All studied patients (100%) were treated with antibiotics. An empirical antibiotics were used to cover Methicillin-resistant Staphylococcus aureus (MRSA) infections in 136 cases (29.6%), methicillin-susceptible Staphylococcus aureus (MSSA) infections in 86 cases (18.7%), atypical pathogen in 174 cases (37.8%), and Pseudomonas infections in 48 cases (10.4%). The most frequently used antibiotics were ceftriaxone/cefotaxime plus macrolide (149 cases; 31%), ceftriaxone/cefotaxime plus quinolone (85 cases; 17.7%), and co-amoxiclav plus fluoroquinolone (78 cases; 16.3%). Imipenem was most frequently used in the ICU (64 cases; 13.3%). CONCLUSION: Despite the antibiotic guidelines clearly stated that antibiotics should only be used in confirmed case of secondary bacterial infections including the COVID-19 patients, our study revealed that the overused of antibiotics remained unchanged. As the misused and overused of antibacterial has been shown to accelerate the emergence and spread of antibacterial resistant, the inappropriate practice should be changed.

Anti-inflammatory roles of type I interferon signaling in the lung.

Excessive or persistent inflammation may have detrimental effects on lung structure and function. Currently, our understanding of conserved host mechanisms that control the inflammatory response remains incompletely understood. In this study, we investigated the role of type I interferon signaling in the inflammatory response against diverse clinically relevant stimuli. Using mice deficient in type I interferon signaling (IFNAR1-/-), we demonstrate that the absence of interferon signaling resulted in a robust and persistent inflammatory response against Pseudomonas aeruginosa, lipopolysaccharide, and chemotherapeutic agent bleomycin. The elevated inflammatory response in IFNAR1-/- mice was manifested as elevated myeloid cells, such as macrophages and neutrophils, in the bronchoalveolar lavage. The inflammatory cell response in the IFNAR1-/- mice persisted to 14 days and there is impaired recovery and fibrotic remodeling of the lung in IFNAR1-/- mice after bleomycin injury. In the Pseudomonas infection model, the elevated inflammatory cell response led to improved bacterial clearance in IFNAR1-/- mice, although there was similar lung injury and survival. We performed RNA sequencing of lung tissue in wild-type and IFNAR1-/- mice after LPS and bleomycin injury. Our unbiased analysis identified differentially expressed genes between IFNAR1-/- and wild-type mice, including previously unknown regulation of nucleotide-binding oligomerization domain (NOD)-like receptor signaling, retinoic acid-inducible gene-I (RIG-I) signaling, and necroptosis pathway by type I interferon signaling in both models. These data provide novel insights into the conserved anti-inflammatory mechanisms of the type I interferon signaling.NEW & NOTEWORTHY Type I interferons are known for their antiviral activities. In this study, we demonstrate a conserved anti-inflammatory role of type I interferon signaling against diverse stimuli in the lung. We show that exacerbated inflammatory response in the absence of type I interferon signaling has both acute and chronic consequences in the lung including structural changes.

Outcomes After Pseudomonas Prosthetic Joint Infections.

Pseudomonas species are a less common but devastating pathogen family in prosthetic joint infections (PJIs). Despite advancements in management, Pseudomonas PJIs remain particularly difficult to treat because of limited antibiotic options and robust biofilm formation. This study aimed to evaluate Pseudomonas PJI outcomes at a single institution and review outcomes reported in the current literature. All hip or knee PJIs at a single institution with positive Pseudomonas culture were evaluated. Forty-two patients (24 hips, 18 knees) meeting inclusion criteria were identified. The primary outcome of interest was infection clearance at 1 year after surgical treatment, defined as reassuring aspirate without ongoing antibiotic treatment. Monomicrobial and polymicrobial infections were analyzed separately. A focused literature review of infection clearance after Pseudomonas PJIs was performed. One-year infection clearance was 58% (n = 11/19) for monomicrobial PJIs and 35% (n = 8/23) for polymicrobial PJIs. Among monomicrobial infections, the treatment success was 63% for patients treated with DAIR and 55% for patients treated with two-stage exchange. Monotherapy with an oral or intravenous antipseudomonal agent (minimum 6 weeks) displayed the lowest 1-year clearance of 50% (n = 6/12). Resistance to antipseudomonal agents was present in 16% (n = 3/19), and two of eight patients with monomicrobial and polymicrobial PJIs developed resistance to antipseudomonal therapy in a subsequent Pseudomonas PJI. Polymicrobial infections (55%) were more common with a mortality rate of 44% (n = 10/23) at a median follow-up of 3.6 years. Pseudomonas infections often present as polymicrobial PJIs but are difficult to eradicate in either polymicrobial or monomicrobial setting. A review of the current literature on Pseudomonas PJI reveals favorable infection clearance rates (63 to 80%) after DAIR while infection clearance rates (33 to 83%) vary widely after two-stage revision.

(046) An Approach to the Thoughtful Selection of Antimicrobial Prophylaxis for Inflatable Penile Prosthesis Surgery

Abstract Introduction There is a growing body of evidence questioning the efficacy of the antibiotic prophylaxis regimens recommended by the American Urological Association (AUA) Best Practice Statement (BPS) for IPP surgery. However, since publication of the BPS the use gentamicin and vancomycin use has increased substantially. This is potentially due to a lack of other specific prophylaxis recommendations making it difficult for surgeons to know which agents to select. Objective We sought to create a simple process to enable surgeons to select an individualized prophylaxis regimen which accounts for local antibiotic resistance patterns. Methods We retrospectively collected IPP infection history from 3 surgeons from 3 different regions of the United States between 2016 and 2021. Local hospital antibiograms were obtained for each surgeons’ institution. Each surgeons IPP infection history was crossed with the resistance patterns on the local antibiograms to identify prophylactic antimicrobial regimens providing the highest level of coverage. Results The organisms causing implant infections for each surgeon during the inclusion period are reported in Table 1. Vancomycin and fluconazole provided excellent Gram-positive and fungal coverage for all surgeons, however Gram-negative coverage varied. Surgeon A had a history of ESBL-producing E. Coli and no infections from Pseudomonas sp. Gentamicin and tobramycin have poor coverage of ESBL-producing E. coli (61% and 52% respectively). However, pipercillin/tazobactam covers 92% of ESBL-producing E. coli. The only Gram-negative organism that pipercillin/tazobactam has worse coverage of than the aminoglycosides is Pseudomonas (gentamicin-92%, tobramycin-96%, pipercilin/tazobactam-80%); however, Surgeon A had no history of Pseudomonas infections. Therefore, the greatest level of coverage can be obtained with vancomycin, pipercillin/tazobactam, and fluconazole. All of Surgeon B’s infections were caused by non-ESBL producing E. coli. Gentamicin, tobramycin, and pipercillin/tazobactam all have excellent coverage of E. coli (95%, 94%, and 95% respectively). Comparing these agents to other common pathogens shows superior coverage of tobramycin over gentamicin and pipercillin/tazobactom for Pseudomonas. The highest level of coverage for Surgeon B can be obtained with vancomycin, tobramycin, and fluconazole. Surgeon C’s infection history has a predominance of Klebsiella sp., but also includes Pseudomonas. Both gentamicin and tobramycin have excellent coverage (>95%) of these Gram-negative organisms. The highest level of coverage can be obtained with vancomycin, an aminoglycoside, and fluconazole. Conclusions The use of local antibiograms and infection history is a simple strategy to tailor prophylaxis regimens to resistance patterns. We found a different regimen to be superior at each institution. Surgeon B’s experience demonstrates that all aminoglycosides may not be equal when factoring in local resistance patterns. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast, Cynosure, Antares Pharma, Clarus Pharmaceuticals, Acerus Pharma, Boston Scientific.

Pseudomonas Infection Outbreak Associated with a Hotel Swimming Pool - Maine, March 2023.

Treated recreational water venues (e.g., pools and hot tubs) located at hotels represent one third of sources of reported treated recreational water-associated outbreaks; when these outbreaks are caused by Pseudomonas aeruginosa, they predominantly occur during January-April. On March 8, 2023, the Maine Center for Disease Control and Prevention (Maine CDC) initiated an investigation in response to reports of illness among persons who had used a swimming pool at hotel A during March 4-5. A questionnaire was distributed to guests who were at hotel A during March 1-7. Among 35 guests who responded, 23 (66%) developed ear pain, rash, or pain or swelling in feet or hands within days of using the pool during March 4-5. P. aeruginosa, a chlorine-susceptible bacterium, was identified in cultures obtained from skin lesions of three patients; a difference of two single nucleotide polymorphisms was found between isolates from two patients' specimens, suggesting a common exposure. Hotel A management voluntarily closed the pool, and Maine CDC's Health Inspection Program identified multiple violations, including having no disinfectant feeder system, all of which had been identified during a previous inspection. Because chlorine had been added to the pool water after the pool was voluntary closed, environmental samples were not collected. The pool remained closed until violations were addressed. Health departments can play an important role in reducing the risk for outbreaks associated with hotel pools and hot tubs. This reduction in risk can be achieved by collaborating with operators to ensure compliance with public health codes, including maintaining chlorine concentration and otherwise vigilantly managing the pool, and by disseminating prevention messages to pool and hot tub users.

Cystic Fibrosis Carrier States Are Associated With More Severe Cases of Bronchiectasis.

People with cystic fibrosis (CF) are at increased risk for bronchiectasis, and several reports suggest that CF carriers may also be at higher risk for developing bronchiectasis. The purpose of this study was to determine if CF carriers are at risk for more severe courses or complications of bronchiectasis. Using MarketScan data (2001-2021), we built a cohort consisting of 105 CF carriers with bronchiectasis and 300 083 controls with bronchiectasis but without a CF carrier diagnosis. We evaluated if CF carriers were more likely to be hospitalized for bronchiectasis. In addition, we examined if CF carriers were more likely to be infected with Pseudomonas aeruginosa or nontuberculous mycobacteria (NTM) or to have filled more antibiotic prescriptions. We considered regression models for incident and rate outcomes that controlled for age, sex, smoking status, and comorbidities. The odds of hospitalization were almost 2.4 times higher (95% CI, 1.116-5.255) for CF carriers with bronchiectasis when compared with non-CF carriers with bronchiectasis. The estimated odds of being diagnosed with a Pseudomonas infection for CF carriers vs noncarriers was about 4.2 times higher (95% CI, 2.417-7.551) and 5.4 times higher (95% CI, 3.398-8.804) for being diagnosed with NTM. The rate of distinct antibiotic fill dates was estimated to be 2 times higher for carriers as compared with controls (95% CI, 1.735-2.333), and the rate ratio for the total number of days of antibiotics supplied was estimated as 2.8 (95% CI, 2.290-3.442). CF carriers with bronchiectasis required more hospitalizations and more frequent administration of antibiotics as compared with noncarriers. Given that CF carriers were also more likely to be diagnosed with Pseudomonas and NTM infections, CF carriers with bronchiectasis may have a phenotype more resembling CF-related bronchiectasis than non-CF bronchiectasis.

Effects of Social Determinants of Health on Clinical Outcomes in Pediatric Cystic Fibrosis Patients

Background and Objective: 
 Advances in the treatment of cystic fibrosis (CF) with cystic fibrosis transmembrane regulator modulators have improved morbidity and mortality, however, clinical outcomes vary among genetically similar patients due to contributions of social determinants of health (SDOH). Pancreatic insufficiency, CF-related diabetes (CFRD), Pseudomonas infections, and lower BMI increase risk of severe lung disease, measured by forced expiratory volume in 1 second (FEV1). This project aims to identify socially vulnerable patients and evaluate the impact of SDOH on clinical outcomes. 
 Methods: 
 From January to July 2023, SDOH screeners were distributed to families of children with CF at Riley Hospital for Children, documenting transportation, housing, food insecurity, insurance, and medication costs. Clinical outcomes for each patient including FEV1% predicted, BMI/WFL percentile, CFRD, hospitalizations, respiratory infections with Pseudomonas aeruginosa, and pancreatic insufficiency within the past 12 months were recorded. Patients were categorized by SDOH vulnerability, and associations with poor clinical outcomes were analyzed using the Chi-squared test of independence. 
 Results: 
 A total of 193 screeners were analyzed: males represented 52.6% of the cohort, 2.60% identified as non-white race, and 3.65% reported Hispanic ethnicity. Overall, 51.8% screened positive for at least one SDOH (SDOH+) and 48.1% screened negative (SDOH-). The average FEV1% predicted decline among SDOH+ patients was 5.79% and 3.51% among SDOH- patients. SDOH+ patients were more likely to have at least a 5% decline in FEV1% predicted (p=0.037) and to be hospitalized due to exacerbations of CF lung disease at least once in the past 12 months (p=0.030). Although low BMI percentile, Pseudomonas infection, and CFRD were not significantly associated with SDOH, socially vulnerable patients demonstrated higher rates of these clinical outcomes. 
 Conclusion and Clinical Implications: 
 SDOH impact CF clinical outcomes. Screeners are effective in identifying socially vulnerable patients and serve as the first step in addressing unmet social needs.

Nutrition optimisation of young tuberculosis patient with poor oral intake

ABSTRACT A 19-year-old female teenager, Chinese, admitted to medical ward on 30 April 2023 with the reason of admission of recurrent disseminated pulmonary tuberculosis (TB) and presented with fever (2/12), cough (3/7), loose stool (1/12), shortness of breath (6/12), lethargy (2/52) and poor oral intake. She had underlying diseases of hypochromic microcytic anemia anaemia 2° iron-deficiency anaemia and folate deficiency, severe hypoalbuminaemia, hospital-acquired pneumonia due to Pseudomonas infection and persistent fever despite being on anti-TB medication. In this case, the patient had already been referred to a dietitian, but a follow-up was needed as she had a loss of appetite and inadequate oral nutrition for a few days. Her calculated body mass index is 16.1 kg/m2 (underweight) and Subjective Global Assessment (SGA) was rated with Grade B (mild-moderate malnutrition) with a history of severe weight loss for the past 1 month. The biochemical data showed abnormal readings of renal profile, albumin and haemoglobin levels.

Dentification of novel potential anti-quorum sensing molecules against LasR of Pseudomonas aeruginosa using in silico approach

Quorum sensing (QS), commonly known as inter-and intracellular communication in bacteria, is accomplished by small, diffusible signaling molecules termed as autoinducers. Numerous virulence factors that are involved in pathogenesis are regulated by QS. It has come to attention as a result of the growing resistance of bacteria to conventional antibiotics, as it applies less to no selective pressure to limit the development of resistance among bacteria. For inhibitors, LasR, a transcription factor that regulates QS in Pseudomonas aeruginosa, is a promising therapeutic target. Hence, the objective of this study is to identify possible LasR inhibitors from natural substances. Virtually 2068 ZINC database compounds were tested against the LasR structure. Following the filtering of suitable compounds using Lipinski's rule and ADME criteria. Depending on binding energy, eight novel potential QS inhibitory agents were identified. To determine how inhibitors and targets bind, structures of LasR-ligand complexes were examined. It is important to note that all of the compounds are structurally distinct from 3-oxo-C12-HSL, a native autoinducer of LasR, which is essential for the activation of LasR dimer that regulates QS system in Pseudomonas aeruginosa. These inhibitors are natural in origin and hence can be very useful in treating Pseudomonas infection; however, we have to properly evaluate their effectiveness, safety, and mode of action, through in vivo and in vitro investigation.

Cloaking antibodies are prevalent in Burkholderia cepacia complex infection and their removal restores serum killing.

The Burkholderia cepacia complex encompasses a group of gram-negative opportunistic pathogens that cause chronic lung infections in people with cystic fibrosis. Distinct from other respiratory pathogens, Burkholderia causes a unique clinical disease in a subset of patients known as 'cepacia syndrome', fulminant pneumonia accompanied by bacteraemia and sepsis with a mortality rate of up to 75%. Due to the bacteraemia associated with this disease, the mechanisms that allow Burkholderia to resist the bactericidal effects of serum complement-depending killing are vital. Antibodies usually promote serum killing; however, we have described 'cloaking antibodies', specific for lipopolysaccharides that paradoxically protect serum-sensitive bacteria from complement-mediated lysis. Cloaking antibodies that protect Pseudomonas aeruginosa have been found in 24%-41% of patients with chronic lung diseases. The presence of these antibodies is also associated with worse clinical outcomes. Here, we sought to determine the relevance of cloaking antibodies in patients with Burkholderia infection. Twelve Burkholderia spp. were isolated from nine pwCF and characterised for susceptibility to healthy control serum. Patient serum was analysed for the titre of the cloaking antibody. The ability of the patient serum to prevent healthy control serum (HCS) killing of its cognate isolates was determined. We found that several of the Burkholderia strains were shared between patients. Ten of the 12 isolates were highly susceptible to HCS killing. Four of nine (44%) patients had cloaking antibodies that protected their cognate strain from serum killing. Depleting cloaking antibodies from patient serum restored HCS killing of Burkholderia isolates. Cloaking antibodies are prevalent in patients with Burkholderia pulmonary infection and protect these strains from serum killing. Removal of cloaking antibodies via plasmapheresis, as previously described for individuals with life-threatening Pseudomonas infection, may be a useful new strategy for those with serious and life-threatening Burkholderia infection.