Introduction Co-infection with Influenza A and Methicillin-Resistant Staphylococcus aureus (MRSA) is a rare but devastating clinical scenario, especially in the elderly with multiple comorbidities. This case report describes a 77-year-old female who rapidly deteriorated from a co-infection of Influenza A and MRSA, resulting in fatal hemorrhagic pneumonia or diffuse alveolar hemmorhage (DAH). This case emphasizes the need for heightened clinical vigilance, prompt diagnosis, and aggressive management in such vulnerable populations (1).

Case Presentation A 77-year-old female with a medical history notable for type 2 diabetes mellitus, hypertension, mild coronary artery disease (clean catheterization in 2021), and recently diagnosed dementia, was transferred to the Emergency Department (ED) from a psychiatric facility. The transfer to ED was prompted by hypoxia, with an oxygen saturation reading in the low 80s. The patient had been admitted to the psychiatric facility just 2 days before her ED admission for suicide evaluation. She did not attempt suicide, but her progressive cognitive decline was causing her significant distress, leading her to have suicide ideation. She had been experiencing mild cough and congestion for several days even prior to her transfer to pschiatric facility. However, on the morning of her admission to the ED, she complianed of significant dyspnea and chest tightness, leading to her transfer to the hospital. Patient was a former smoker but quit smoking several years ago. As per her daughter she had been upto date on her appointments with her PCP and was generally healthy and compliant with all her medications. She was taking baby aspirin but denied taking any blood thinners or chemotherapy medications.

Upon arrival at the ED, the patient was found to be confused and somnolent but arouseable. She was noted to be in significant distress due to her acute hypoxic respiratory failure and was immediately placed on BiPap. On admission, she was febrile with a temperature of 100 F, tachycardic with a heart rate of 99 beats per minute and a blood pressure of 123/66. Patient denied any hemoptysis or bloody emesis but was noted to have dried bloody secretions in her mouth. On lung examination, she had coarse crackles and wheezes bilaterally, more pronounced on the right side. Laboratory tests showed initial hemoglobin of 13.3 g/dL, severe leukopenia (with a total white blood count of 1.88 k/uL and absolute neutrophil counT of 0.60 k/uL) and bandemia (total band percentage of 19.0). The platelet count was 136 k/uL with initial lactate of 3.64 which trended upto 4.64 mmol/L and a procalcitonin level of 47.26 ng/ml. Coagulation profile showed an international (INR) of 1.36 and a prothrombin time (PT) of 16.5 and a partial thrombolastin time (PTT) of 29.4. Serum and urine toxicology were negative and salycilate, acetaminophen and alcohol levels were within normal limits. Radiological imaging revealed a complete whiteout of the right mid to lower lung lobe, concerning for right lobe pneumonia. The patient’s condition rapidly deteriorated; she became hypotensive and unresponsive, necessitating emergent intubation. During intubation, blood was observed in her lungs, prompting an emergent bedside bronchoscopy which confirmed active pulmonary hemorrhage.

The patient was septic on arrival but rapidly developed shock and was immediately transferred to the Intensive Care Unit (ICU) where she was started on two vasopressors to manage her hypotension. She was also started on broad spectrum antibiotics with vancomycin and meropenem. While attempts were being made to stop her alveolar hemorrage via bedside bronchoscopy, her Influenza A nasal swab came back positive. She was also started on oseltamivir. However, despite aggressive measures, including multiple runs of epinephrine and cold saline to control the alveolar bleeding, the hemorrhage continued unabated. The patient was deemed too unstable for transfer to Interventional Radiology for embolization. Her condition remained refractory to all interventions and she was eventually transitioned to comfort care, passing away shortly thereafter.

Postmortem laboratory investigations which included blood cultures, bronchoalveolar lavage (BAL), revealed a co-infection with Influenza A and MRSA. This combination is known to be particularly lethal due to the synergistic pathogenic mechanisms leading to severe necrotizing hemorrhagic pneumonia .(1,3) The presence of Influenza A likely predisposed the patient to a secondary bacterial infection with MRSA, creating a cascade of respiratory compromise and hemorrhagic manifestations and that proved impossible to halt with available medical interventions (1).

Discussion The case of our patient illustrates the severe consequences of co-infection with Influenza A and MRSA, particularly in an elderly individual with multiple comorbid conditions. Influenza A infection can impair the respiratory epithelium, reduce immune responses, and create an environment conducive to secondary bacterial infections, such as MRSA (4) . Once established, MRSA can cause necrotizing pneumonia, characterized by rapid tissue destruction, extensive inflammation, and hemorrhage (3) .

Elderly patients, particularly those with underlying comorbidities like diabetes mellitus, hypertension, coronary artery disease, and cognitive impairments, are at higher risk of severe outcomes from respiratory infections (4). The immunosuppressive effects of diabetes and advanced age can exacerbate the severity of infections and impair the patient's ability to mount an effective immune response (4) . The pathophysiology involves several mechanisms: Influenza A virus damages the respiratory epithelium, reducing mucociliary clearance and creating a nidus for bacterial colonization and invasion (4). MRSA exploits this breach, leading to severe secondary infections. MRSA produces several virulence factors, including Panton-Valentine leukocidin (PVL), which can cause necrotizing pneumonia with tissue necrosis and hemorrhage (3) . The combination of these pathogens leads to a severe inflammatory response, often resulting in alveolar hemorrhage, rapid respiratory failure, and high mortality (1) . However, the absence of these virulence factors does not neceassary decrease the risk of developing complications. For instance, a young healthy 46-year-old woman succumbed to death within a few hours of arrival due to co-infection, even though the PCR assay did not detect PVL. ( number)

Managing such cases presents significant challenges. Early recognition and differentiation between primary viral pneumonia and secondary bacterial infections are crucial (4) . Empiric broad-spectrum antibiotics, including coverage for MRSA, are recommended in severe cases of community-acquired pneumonia during influenza season (4) . However, rapid progression to hemorrhagic pneumonia, as seen in this patient, limits the efficacy of medical management (3). Despite advanced medical interventions, the rapid progression and severe hemorrhagic manifestations in such co-infections often outpace therapeutic measures. The case underscores the need for aggressive early treatment strategies and the potential role of antiviral and antibacterial prophylaxis in high-risk populations (2) .

Prevention of such fatal outcomes requires a multifaceted approach. Influenza vaccination is critical in preventing primary viral infections. Annual vaccination can reduce the incidence and severity of influenza infections (4) . Strict infection control practices in healthcare settings, especially in long-term care and psychiatric facilities, are essential to prevent the spread of MRSA and other nosocomial pathogens (4). Prompt identification and isolation of infected individuals can prevent the spread of influenza and MRSA (4) . Early use of antiviral medications for influenza and empiric antibacterial therapy, including MRSA coverage, in suspected severe cases of respiratory infection can mitigate disease progression (2).

Further research is needed to better understand the synergistic effects of influenza and MRSA co-infection and to develop more effective treatment protocols (1). Increased awareness among clinicians about the potential for such severe co-infections can lead to earlier diagnosis and intervention, potentially improving outcomes (2) . The role of steriods in such cases also needs to be studied further. Despite administeration of stress-dose steriod in some cases patients condition continued to deteriorate. The same is true for the use of ECMO. Given the severity of pulmonary hemorrage and coagulopathy patients develop, they are not considered candidates for ECMO.

Conclusion This case highlights the lethal potential of co-infection with Influenza A and MRSA, particularly in elderly patients with multiple comorbidities. The rapid progression to hemorrhagic pneumonia, as demonstrated, poses formidable challenges to clinical management. Heightened vigilance, early diagnosis, and aggressive treatment are crucial. Preventive measures, including vaccination and strict infection control practices, are paramount in protecting vulnerable populations. Further research and increased clinical awareness are necessary to improve outcomes in such devastating cases (1) .

References Toolsie, O., Tehreem, A., & Diaz-Fuentes, G. (2019). "Influenza A pneumonia associated with diffuse alveolar hemorrhage." American Journal of Case Reports, 20, 592-596.

Randolph, A. G., Vaughn, F., Sullivan, R., Rubinson, L., Thompson, B. T., Yoon, G., ... & Project, N. E. C. C. (2011). "Critically ill children during the 2009–2010 influenza pandemic in the United States." Pediatrics, 128(6), e1450-e1458.

Klugman, K. P., & Madhi, S. A. (2012). "Rapidly lethal necrotizing hemorrhagic pneumonia." Critical Care Medicine, 40(12), 1235-1244.

Chakrabarti, B., Davies, P. D. O., & Dewan, P. (2017). "How a mild influenza B infection can kill: A case of necrotizing pneumonia." Lung India, 34(5), 448-450.