Severe necrotizing tracheobronchitis caused by influenza B and methicillin-resistant Staphylococcus aureus co-infection in an immunocompetent patient.

PURPOSE AND METHOD: Necrotizing tracheobronchitis is a rare clinical entity presented as a necrotic inflammation involving the mainstem trachea and distal bronchi. We reported a case of severe necrotizing tracheobronchitis caused by influenza B and methicillin-resistant Staphylococcus aureus (MRSA) co-infection in an immunocompetent patient. CASE PRESENTATION: We described a 36-year-old man with initial symptoms of cough, rigors, muscle soreness and fever. His status rapidly deteriorated two days later and he was intubated. Bronchoscopy demonstrated severe necrotizing tracheobronchitis, and CT imaging demonstrated multiple patchy and cavitation formation in both lungs. Next-generation sequencing (NGS) and bronchoalveolar lavage fluid (BALF) culture supported the co-infection of influenza B and MRSA. We also found T lymphocyte and NK lymphocyte functions were extremely suppressed during illness exacerbation. The patient was treated with antivirals and antibiotics including vancomycin. Subsequent bronchoscopy and CT scans revealed significant improvement of the airway and pulmonary lesions, and the lymphocyte functions were restored. Finally, this patient was discharged successfully. CONCLUSION: Necrotizing tracheobronchitis should be suspected in patients with rapid deterioration after influenza B infection. The timely diagnosis of co-infection and accurate antibiotics are important to effective treatment.

Changing trends in clinical characteristics and in-hospital mortality of patients with infective endocarditis over four decades.

BACKGROUND: Infective endocarditis continues to be a significant concern and may be undergoing an epidemiological transition. METHODS: Were studied 1804 consecutive episodes of infective endocarditis between 1978 and 2022. The mean age was 48 ( ± 19), and 1162 (64%) patients were male. Temporal trends in demographic data, comorbidities, predisposing conditions, microorganisms, complications and in-hospital death have been studied over the decades (1978-1988, 1989-1999, 2000-2010 and 2011-2022). The outcomes and clinical characteristics were modeled using nonlinear cubic spline functions. FINDINGS: Valve surgery was performed in 50% of the patients and overall in-hospital mortality was 30%. From the first to the fourth decade studied, the average age of patients increased from 29 to 57 years (p < 0.001), with significant declines in the occurrence of rheumatic valvular heart disease (15% to 6%; p < 0.001) and streptococcal infections (46% to 33%; p < 0.001). Healthcare-associated infections have increased (9% to 21%; p < 0.001), as have prosthetic valve endocarditis (26% to 53%; p < 0.001), coagulase-negative staphylococcal infections (4% to 11%; p < 0.001), and related-complications (heart failure, embolic events, and perivalvular abscess; p < 0.001). These changes were associated with a decline in adjusted in-hospital mortality from 34% to 25% (p = 0.019). INTERPRETATION: In the 44 years studied, there was an increase in the mean age of patients, healthcare-related, prosthetic valve, coagulase-negative staphylococci/MRSA infections, and related complications. Notably, these epidemiological changes were associated with a decline in the adjusted in-hospital mortality.

Infectious aortitis and managing it at a community military hospital.

Infectious aortitis is a rare disease process which can be of fungal, viral or bacterial aetiology. This disease process is often incidentally found during concomitant infectious processes, likely due to haematogenous spread. Common sources are from cardiac, genitourinary and gastroenterologic sources. CT imaging of the aorta is essential in identifying physiological changes-wall thickness changes, ectasia and stenosis. We present a case of a female in her early 60s with a medical history of cardiomyopathy with heart failure and reduced ejection fraction, who was initially admitted for acute cholecystitis complicated by the development of gallstone pancreatitis. Imaging evaluation incidentally noted findings consistent with aortitis with a penetrating ulcer, and blood cultures were positive for Staphylococcus aureus bacteraemia, confirming her diagnosis of infectious aortitis. She was started on intravenous antibiotics, required preoperative nutritional optimisation, and subsequently underwent an open aortic resection and aortoiliac reconstruction with rifampin-soaked Dacron graft.

Endogenous Endophthalmitis Secondary to Infected Cutaneous Basal Cell Carcinoma: A Case Report.

INTRODUCTION: Endogenous endophthalmitis (EE) is a severe intraocular infection due to hematogenous spread of bacteria from an extraocular site. Recognition of the primary source of hematogenous spread of bacteria is essential to establish an adequate therapy and avoid other major complications. Infected cutaneous tumor has never been reported as a possible source of EE. PURPOSE: To describe the first case of EE due to hematogenous spread of methicillin-sensitive Staphylococcus aureus from an infected cutaneous basal cell carcinoma. Systemic antibiotic therapy and surgical excision of the cutaneous lesion were performed. CONCLUSION: Severe and long-standing skin infections should be considered as a rare cause of EE.

The impact of wound pH on the antibacterial properties of Medical Grade Honey when applied to bacterial isolates present in common foot and ankle wounds. An in vitro study.

BACKGROUND: Diabetic foot ulcers (DFUs) and post-surgical wound infections are amongst the most troublesome complications of diabetes and following foot and ankle surgery (FAS) respectively. Both have significant psychosocial and financial burden for both patients and the healthcare system. FAS has been reported to have higher than average post-surgical infections when compared to other orthopaedic subspecialties. Evidence also indicates that patients with diabetes and other co morbidities undergoing FAS are at a much greater risk of developing surgical site infections (SSIs). With the growing challenges of antibiotic resistance and the increasingly high numbers of resilient bacteria to said antibiotics, the need for alternative antimicrobial therapies has become critical. AIM: The aim of this study was to investigate the use of medical grade honey (MGH) when altered to environments typically present in foot and ankle wounds including DFUs and post-surgical wounds (pH6-8). METHODS: MGH (Activon) was altered to pH 6, 7 and 8 and experimental inoculums of Pseudomonas aeruginosa (NCTC10782), Escherichia coli, (NCTC10418), Staphylococcus aureus (NCTC10655) and Staphylococcus epidermidis (NCTC 5955) were transferred into each pH adjusted MGH and TSB solution and the positive and negative controls. RESULTS: MGH adjusted to various pH values had the ability to reduce bacteria cell survival in all pH variations for all bacteria tested, with the most bacterial reduction/elimination noted for Staphylococcus epidermidis. No correlations were noted among the pH environments investigated and the colony counts, for which there were small amounts of bacteria survived. CONCLUSION: This research would indicate that the antibacterial properties of honey remains the same regardless of the pH environment. MGH could therefore potentially be considered for use on non-infected foot and ankle wounds to reduce the bacterial bioburden, the risk of infections and ultimately to improve healing outcomes.

Macrophage activation syndrome induced by Staphylococcus Epidermidis in a pediatric patient with cystic fibrosis and familial Mediterranean fever.

Staphylococcus epidermidis (S. epidermidis) is the most frequently isolated member of the coagulase-negative staphylococci, which colonizes the skin and mucous membranes of the human body. Despite being a component of the normal flora, S. epidermidis can act as an opportunistic pathogen and is frequently implicated in both bacterial and nosocomial infections. Macrophage activation syndrome (MAS) is a rare but potentially fatal disease that occurs as a result of increased activation and proliferation of T lymphocytes and macrophages in response to infections and immune mediated diseases. It is very rare in patients with cystic fibrosis. Here we report a case of an 8-year-old girl with cystic fibrosis and familial Mediterranean fever who developed MAS after contracting a S. epidermidis infection.

Unilateral Osler nodes, Janeway lesions and splinter haemorrhages associated with surgical arterio-venous fistula infection: a case report.

BACKGROUND: Osler's nodes, Janeway lesions and splinter haemorrhages are cutaneous manifestations of infective endocarditis. They occur due to vascular occlusion by septic emboli and a resulting localized vasculitis. They are usually bilateral. We report a case of unilateral Osler's nodes, Janeway lesions and splinter haemorrhages due to an ipsilateral surgical arterio-venous fistula infection. CASE PRESENTATION: A fifty-two-year-old Sri Lankan female with end stage kidney disease presented with fever for five days with blurred vision, pain and redness of the right eye. She had a left brachio-cephalic arterio-venous fistula (AVF) created one month back. She complained of a foul-smelling discharge from the surgical site for past three days. Redness of the right eye with a hypopyon was noted. AVF site over the left cubital fossa was infected with a purulent discharge. Osler's nodes, Janeway lesions and splinter haemorrhages were noted in the distal fingers, thenar and hypothenar eminences of the left hand. Right hand and both feet were normal. No cardiac murmurs were heard. Blood cultures, vitreous sample cultures and pus cultures from the fistula site were all positive for methicillin sensitive Staphylococcus aureus. Infective endocarditis was excluded by a trans-oesophageal echocardiogram. She was treated with IV flucloxacillin and surgical excision of the AVF. CONCLUSION: Infections of AVF can result in septic emboli formation which can have both anterograde arterial embolization and retrograde venous embolization. Arterial embolization can result in unilateral Osler's nodes, Janeway lesions and splinter haemorrhages. Venous embolization can cause metastatic infections in the systemic and pulmonary circulations.

Ethnic differences in staphylococcus aureus acquisition in cystic fibrosis.

BACKGROUND: Hispanic people with CF (pwCF) have increased morbidity than non-Hispanic White pwCF, including increased risk of Pseudomonas aeruginosa. We aimed to determine if Staphylococcus aureus (S. aureus) acquisition varies between Hispanic and non-Hispanic White pwCF. METHODS: This longitudinal cohort study of pwCF ages 0-25 years in the CF Foundation Patient Registry compared acquisition of methicillin-sensitive S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), persistent MRSA between Hispanic and non-Hispanic White pwCF. Risk of acquisition was assessed by Kaplan-Meier survival curves and its association with ethnicity was evaluated using Cox regressions. Adjusted associations were evaluated using multivariate Cox models adjusting for sex, age of entry into CFFPR, CFTR variant severity, pancreatic insufficiency, CF-related diabetes, maternal education, insurance status. RESULTS: Of 10,640 pwCF, 7.5% were Hispanic and 92.5% were non-Hispanic White. Hispanic pwCF had a 19% higher risk of acquiring MSSA (HR 1.19, 95% CI 1.10-1.28, p<0.001) and 13% higher risk of acquiring MRSA (HR 1.13, 95% CI 1.02-1.26, p = 0.02) than non-Hispanic White pwCF. The difference in persistent MRSA between ethnicities did not reach statistical significance. After adjusting for confounding variables, only the risk of MSSA was significantly associated with ethnicity. Compared to non-Hispanic White pwCF, Hispanic pwCF acquired MSSA and MRSA at younger median ages (4.9 vs. 3.8 years (p<0.001), 22.4 vs. 20.8 years (p = 0.02). CONCLUSION: Hispanic pwCF <25 years of age have an increased risk of acquiring MSSA and acquired MSSA and MRSA at an earlier age. Differences in S. aureus acquisition may contribute to increased morbidity in Hispanic pwCF.

Bacterial endocarditis following COVID-19 infection: two case reports.

BACKGROUND: COVID-19, an emerging disease raised as a pandemic, urgently needed treatment choices. Some options have been confirmed as lifesaving treatments, but long-term complications must be clearly illustrated. Bacterial endocarditis is a less frequent disease among patients infected with SARS_COV_2 compared to other cardiac comorbidities in these patients. This case report discusses bacterial endocarditis as a potential adverse effect after administering tocilizumab, corticosteroids, and COVID-19 infection. CASE PRESENTATION: In the first case, a 51-year-old Iranian female housewife was admitted to the hospital with fever, weakness, and monoarthritis symptoms. The second case is a 63-year-old Iranian woman who is a housewife admitted with weakness, shortness of breath, and extreme sweating. Both cases tested positive for Polymerase chain reaction (PCR) less than one month ago and were treated with tocilizumab and corticosteroid. Both patients were suspected of infective endocarditis. Methicillin-resistant Staphylococcus aureus (MRSA) was detected in the blood cultures of both patients. The diagnosis of endocarditis is confirmed for both cases. Cases are subjected to open-heart surgery, a mechanical valve is placed, and they are treated with medication. In subsequent visits, their condition was reported to be improving. CONCLUSION: Adjacent to cardiovascular inclusion as COVID-19 disease complications, secondary infection taken after the organisation of immunocompromising specialists can result in basic maladies and conditions counting infective endocarditis.

Impact of transfer to reference centres and surgical timing on the prognosis of surgically treated patients with infective endocarditis: a prospective multi-centre cohort study.

OBJECTIVES: To compare outcomes in patients with infective endocarditis (IE) first treated in secondary hospitals and then transferred to reference centres for surgery with those in patients diagnosed in reference centres, and to evaluate the impact of surgery timing on prognosis. METHODS: Analysis of a prospective cohort of patients with active IE admitted to three reference centres between 1996 and 2022 who underwent cardiac surgery in the first month after diagnosis. Multi-variable analysis was performed to evaluate the impact of transfer to reference centres and time to surgery on 30-day mortality. Adjusted ORs with 95% CIs were calculated. RESULTS: Amongst 703 patients operated on for IE, 385 (54.8%) were referred cases. All-cause 30-day mortality did not differ significantly between referred patients and those diagnosed at reference centres (102/385 [26.5%] vs. 78/385 [24.5%], respectively; p 0.552). Variables independently associated with 30-day mortality in the whole cohort were diabetes (OR, 1.76 [95% CI, 1.15-2.69]), chronic kidney disease (OR, 1.83 [95% CI, 1.08-3.10]), Staphylococcus aureus (OR, 1.88 [95% CI, 1.18-2.98]), septic shock (OR, 2.76 [95% CI, 1.67-4.57]), heart failure (OR, 1.41 [95% CI, 0.85-2.11]), acute renal failure before surgery (OR, 1.76 [95% CI, 1.15-2.69]), and the interaction between transfer to reference centres and surgery timing (OR, 1.18 [95% CI, 1.03-1.35]). Amidst referred patients, time from diagnosis to surgery longer than a week was independently associated with 30-day mortality (OR, 2.19 [95% CI, 1.30-3.69]; p 0.003). CONCLUSION: Among referred patients, surgery performed >7 days after diagnosis was associated with two-fold higher 30-day mortality.

Clinical pointers in Prevotella septic arthritis of the hip: a case report.

BACKGROUND: Infective arthritis is an orthopaedic surgical emergency. Staphylococcus aureus remains the commonest causative bacteria across all age groups. Prevotella spp. as a cause of infective arthritis is extremely rare. CASE REPORT: We present our case of a 30-year-old African male patient who presented with mild signs of infective arthritis of the left hip. His risk factors were his background retroviral disease, intravenous drug abuse, and a previous episode of left hip arthrotomy which healed expectantly with intervention. The current presentation was treated with arthrotomy of the hip, fluid lavage, and skeletal traction based on our clinical findings and the rarity of the presentation was seen to be mobilising non-weight bearing with crutches, and pain-free on the left hip. CONCLUSION: A high index of suspicion for Prevotella Septic Arthritis (PSA) should be exercised when treating infective arthritis patients with background joint arthropathies, and intravenous drug abuse, especially in individuals with significant immunosuppression and/or recent tooth extraction. Fortunately, although rare an entity, good outcomes can be expected with early diagnosis and classic treatment principles of joint decompression and lavage as well as guided antibiotic therapy.

Shock séptico en niños con bacteriemia por Staphylococcus aureus de la comunidad en un hospital pediátrico de alta complejidad / Septic shock in children with community acquired Staphylococcus aureus bacteremia in a high complexity pediatric hospital

INTRODUCCIÓN: La información disponible sobre los factores de riesgo para el desarrollo de shock séptico es escasa, especialmente en población pediátrica. OBJETIVO: Describir las características epidemiológicas y clínicas de los niños con bacteriemia adquirida en la comunidad por Staphylococcus aureus y comparar las características de los pacientes con y sin shock séptico. PACIENTES Y MÉTODOS: Estudio de cohorte retrospectivo. Criterios de inclusión: niños entre 30 días y 16 años de edad, internados en el Hospital de Pediatría Juan P. Garrahan entre enero de 2017 y diciembre de 2019 por infecciones adquiridas en la comunidad con desarrollo de S. aureus en hemocultivos. Criterios de exclusión: antecedente de internación dentro de los 3 meses previos al ingreso, vivir en una comunidad cerrada, presencia de catéter de larga permanencia, dispositivos intraventriculares o intraperitoneales. Análisis estadístico: STATA 16. RESULTADOS: Se incluyeron 142 niños. 21 niños (15%) presentaron shock séptico. En el análisis multivariado, se asociaron con shock séptico, la bacteriemia persistente (OR 7,15; IC95% 4,39-23,81; p: 0,001) y el foco secundario de infección (OR 6,72; IC 95% 2,02-22,2; p 0,002). La mortalidad relacionada con la infección fue 3,5% (5 pacientes). CONCLUSIONES: El shock séptico se asoció con la bacteriemia persistente y la presencia de focos secundarios de infección.

BACKGROUND: Available information about risk factors for the development of septic shock is scarce, especially in the pediatric population. AIM: To describe the epidemiological and clinical characteristics of children with community-acquired Staphylococcus aureus bacteremia and to compare the characteristics of children with and without septic shock. METHODS: Retrospective cohort study. Inclusion criteria: Children between 30 days and 16 years old, hospitalized in the Juan P. Garrahan Pediatric Hospital between January 2017 and December 2019 for community-acquired infections with S. aureus isolation in blood cultures. Exclusion criteria: History of hospitalization within 3 months prior to admission, living in a closed community, presence of long-term catheter, intraventricular or intraperitoneal devices. Statistical analysis: STATA 16. RESULTS: 142 children were included. 21 children (15%) experienced septic shock. On multivariate analysis, persistent bacteremia (OR 7.15, 95% CI 4.39-23.81, p: 0.001) and secondary focus of infection (OR 6.72, 95% CI 2.02-22.2, p 0.002) were associated with septic shock. The infection-related mortality rate was 3.5% (5 patients). CONCLUSIONS: Septic shock was associated with persistent bacteremia and the presence of secondary foci of infection.

Rat model of recalcitrant prosthetic joint infection using biofilm inocula.

Prosthetic joint infection (PJI) is a rare but devastating complication of joint arthroplasty. Biofilm formation around the prosthesis confers tolerance to antibiotics so that treatment is challenging. Most animal models of PJI use planktonic bacteria to establish the infection which fails to reproduce the pathology of chronic infection. We aimed to establish a rat model of Staphylococcus aureus PJI in male Sprague-Dawley rats using biofilm inocula and demonstrate its tolerance to frontline antibiotics. Pilot studies indicated that infection could be introduced to the knee joint by a biofilm-coated pin but that handling the prosthetic without disturbing the biofilm was difficult. We, therefore, developed a pin with a slotted end and used a miniature-biofilm reactor to develop mature biofilm in this niche. These biofilm-laden pins consistently produced infection of the bone and joint space. Treatment with high dose cefazolin, 250 mg/kg, starting the day of surgery reduced or cleared pin-adherent bioburden within 7 days, however when escalation from 25 to 250 mg/kg cefazolin treatment was delayed for 48 h, rats were unable to clear the infection. To track infections, we used bioluminescent bacteria, however, the bioluminescent signal did not accurately track the degree of infection in the bone and joint space as the signal did not penetrate the bone. In conclusion, we demonstrate that using a custom prosthetic pin, we can generate biofilm in a specific niche using a novel bioreactor setup and initiate a rat PJI that rapidly develops tolerance to supra-clinical doses of cefazolin.

Severe atypical Lemierre syndrome caused by methicillin-sensitive Staphylococcus aureus: Two pediatric case reports.

BACKGROUND: Lemierre syndrome is typically associated with ear, nose, and throat (ENT) infections caused by Fusobacterium necrophorum. Since 2002, cases of atypical Lemierre-like syndrome secondary to Staphylococcus aureus have been reported. CASES: We report two pediatric cases of atypical Lemierre syndrome with a similar presentation: exophthalmia, absence of pharyngitis, metastatic lung infection, and intracranial venous sinus thrombosis. Both patients had a favorable outcome following treatment with antibiotics, anticoagulation, and corticosteroids. CONCLUSION: Regular therapeutic monitoring of antibiotic levels helped to optimize antimicrobial treatment in both cases.

Clinical significance of concomitant bacteriuria in patients with Staphylococcus aureus bacteraemia.

This retrospective study, conducted at Lausanne University Hospital (2015-2021), compared Staphylococcus aureus bacteraemia (SABA) patients with or without concomitant bacteriuria (SABU). Among 448 included bacteraemic patients, 62 (13.8%) had S. aureus concurrently isolated from urine. In multivariate analysis, there was a significant difference in the odds of community-onset bacteraemia (P 0.030), malignancy (P 0.002), > 1 pair of positive blood cultures (P 0.037), and persistent bacteraemia for at least 48 h (P 0.045) in patients with concurrent SABU. No difference concerning mortality was found. On the other hand, SABU was associated with higher rates of SABA recurrence after antibiotic cessation.

Nosocomial meningitis caused by Staphylococcus haemolyticus in a child with neutropenia in the absence of intracranial devices: a case report.

BACKGROUND: Coagulase-negative staphylococci can cause hospital-acquired infections, especially in immunocompromised hosts. Bacterial meningitis is a potentially fatal infection of the central nervous system, causing high mortality and morbidity. In general, the causative agents of meningitis, coagulase-negative staphylococci, are associated with direct implantation of a foreign body and the presence of a cerebrospinal fluid (CSF) shunt. Here, we describe a case of nosocomial meningitis caused by Staphylococcus haemolyticus in a child with neutropenia who had no intracranial foreign devices. CASE PRESENTATION: A 15-year-old boy with relapsed acute myeloid leukemia undergoing chemotherapy through a central venous catheter developed fever on Day 13 post-initiation of chemotherapy. There was no history of implantation of neurosurgical devices. Two blood cultures obtained on Day 14 were positive for Staphylococcus haemolyticus. Clinical improvement was noted, and treatment with vancomycin and removal of the central venous catheter resulted in negative repeat blood cultures on Day 18. However, the patient developed a tendency for somnolence and improper speech, along with persistent fever on Day 26. A lumber puncture was performed on Day 27, resulting in positive culture of Staphylococcus haemolyticus. He was diagnosed with meningitis and the dosage of vancomycin was increased. A repeat CSF culture was positive for Staphylococcus haemolyticus on Day 40, so oral rifampicin was added. CSF findings on Day 46 revealed a low concentration of vancomycin, and treatment was switched from vancomycin plus rifampicin to linezolid. After Day 46, four subsequent cerebrospinal fluid tests of the CSF showed no growth of Staphylococcus haemolyticus. The patient's symptoms were improved on Day 52. Brain and spinal magnetic resonance images was taken and it showed no abnormalities. Linezolid was continued until Day 72. The patient was discharged without any complications on Day 72. CONCLUSIONS: To the best of our knowledge, this is the first reported case of Staphylococcus haemolyticus meningitis in a patient without a neurosurgical device. Typical symptoms or signs may be absent in a patient with meningitis who also has neutropenia. Repeated tests of the CSF, and prolonged duration of antibiotics should be considered if atypical pathogens are detected in immunocompromised hosts.

Synergistic effects of length of stay and prior MDRO carriage on the colonization and co-colonization of methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and carbapenemase-producing Enterobacterales across healthcare settings.

OBJECTIVE: To characterize the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and carbapenemase-producing Enterobacterales (CPE) co-colonization and to compare risk factors between healthcare facility types. DESIGN, SETTING, AND PARTICIPANTS: We conducted a 3-year cross-sectional study among patients admitted to an acute-care hospital (ACH) and its 6 closely affiliated intermediate- and long-term care facilities (ILTCFs) in Singapore in June and July of 2014-2016. METHODS: Specimens were concurrently collected from nares, axillae, and groins for MRSA detection, and from rectum or stool for VRE and CPE detection. Co-colonization was defined as having >1 positive culture of MRSA/VRE/CPE. Multinomial logistic regression was performed to determine predictors of co-colonization. RESULTS: Of 5,456 patients recruited, 176 (3.2%) were co-colonized, with higher prevalence among patients in ITCFs (53 of 1,255, 4.2%) and the ACH (120 of 3,044, 3.9%) than LTCFs (3 of 1,157, 0.3%). MRSA/VRE was the most common type of co-colonization (162 of 5,456, 3.0%). Independent risk factors for co-colonization included male sex (odds ratio [OR], 1.96; 95% confidence interval [CI], 1.37-2.80), prior antibiotic therapy of 1-3 days (OR, 10.39; 95% CI, 2.08-51.96), 4-7 days (OR, 4.89; 95% CI, 1.01-23.68), >7 days (OR, 11.72; 95% CI, 2.81-48.85), and having an open wound (OR, 2.34; 95% CI, 1.66-3.29). Additionally, we detected the synergistic interaction of length of stay >14 days and prior multidrug-resistant organism (MDRO) carriage on co-colonization. Having an emergency surgery was a significant predictor of co-colonization in ACH patients, and we detected a dose-response association between duration of antibiotic therapy and co-colonization in ILTCF patients. CONCLUSIONS: We observed common and differential risk factors for MDRO co-colonization across healthcare settings. This study has identified at-risk groups that merit intensive interventions, particularly patients with prior MDRO carriage and longer length of stay.

PI3K/AKT-mediated autophagy inhibition facilitates mast cell activation to enhance severe inflammatory lung injury in influenza A virus- and secondary Staphylococcus aureus-infected mice.

Influenza A virus infection causes considerable morbidity and mortality each year globally, and secondary bacterial infection further exacerbates the severity and fatality of the initial viral infection. Mast cells have substantial roles in protecting the respiratory tract mucosa, while their role in viral and bacterial co-infection remains unclear. The present study revealed that secondary Staphylococcus aureus infection significantly aggravated the activation of mast cells during the initial H1N1 infection both in vivo and in vitro, which was closely related to the increased inflammatory lung injury and mortality. Meanwhile, the secondary S. aureus infection suppressed autophagy and promoted inflammatory mediators released by mast cells through activating the PI3K/Akt signaling pathway. Blocking PI3K/Akt pathway by LY294002, an inhibitor of Akt phosphorylation, could rescue autophagy and inhibit the release of inflammatory mediators. Furthermore, based on the influenza A viral and secondary bacterial infected mice model, we showed that the combination of LY294002 and antiviral drug oseltamivir could effectively reduce the inflammatory damage and pro-inflammatory cytokines releasing in lungs, recovering body weight loss and improving the survival rate from the co-infections. In conclusion, secondary bacterial infection can inhibit autophagy and stimulate mast cell activation through the PI3K/Akt pathway, which might explain why secondary bacterial infection would cause severe and fatal consequences following an initial influenza A viral infection.