Abstract Introduction Opportunistic infections arise when typically, non-pathogenic organisms become virulent in hosts with impaired immunity. While such infections commonly affect immunocompromised patients, they may also occur in the elderly due to immunosenescence—the age-related decline of immune function. We describe an unusual case of severe pneumonia caused by a co-infection in a 90-year-old man without known comorbidities or immunosuppression, highlighting the potential role of microbial synergy and immunosenescence in disease severity. Description A 90-year-old male, living in the central mountain area of Puerto Rico, with no medical history was admitted to the ICU with worsening dyspnea, chest pain, palpitations, and a chronic dry cough on a HFNC of 60L and 50% FIO2. He denied fever, recent travel, medications, or steroid use. Examination revealed tachycardia, diffuse crackles, and cervical lymphadenopathy. Laboratory findings included leukocytosis (24.6 K/uL), elevated lactate (5.1 mmol/L), and procalcitonin (4.2 ng/mL). Chest CT showed a left cavitary lesion (2.2 × 1.5 × 2.1 cm), loculated pleural effusion, and pneumothorax (Figure 1). A large-bore chest tube was inserted. Bronchoscopy revealed tracheobronchomalacia with erythema and mucus plugging. BAL samples demonstrated strongly acid-fast bacilli consistent with Mycobacterium tuberculosis complex, weakly acid-fast Nocardia, and Aspergillus fumigatus growth. He was initiated on Isoniazid, Rifampin, Pyrazinamide, Ethambutol, and empiric Vancomycin, later adjusted to Meropenem and TMP-SMX for additional coverage. Antifungal therapy was withheld given repeat negative galactomannan, antigen, and PCR results, and drug interactions. Two weeks into therapy, acid-fast bacilli persisted. He developed drug-induced hepatotoxicity and SIADH, prompting regimen changes to Minocycline, Rifapentine, Imipenem, and later Bedaquiline, Pretomanid, and Linezolid. Despite temporary improvement, he developed septic shock secondary to Candida albicans fungemia and ultimately worsened despite maximal medical therapy. Goals of care were discussed; and the patient requested hospice care. Discussion This case represents a rare opportunistic pulmonary co-infection causing severe respiratory failure in a host without classical immunodeficiency, underscoring the impact of microbial synergy and immunosenescence. The coexistence of M. tuberculosis and Nocardia likely intensified cavitary destruction, while fungal elements further impaired mucosal defense, amplifying pathogenicity and resistance. Synergistic microbial interactions make diagnosis challenging, mimic multidrug-resistant infections, and complicate therapeutic options. Advanced age likely contributed to reduced innate and adaptive immunity, creating an environment for pathogen cooperation and persistence. Clinicians should maintain high suspicion for polymicrobial synergy in elderly patients with severe or refractory pneumonia. Early comprehensive microbiologic evaluation and recognition of immunosenescence are critical for optimizing individualized treatment and improving outcomes. This abstract is funded by: None
Cruz et al. (Fri,) studied this question.