A 21-year-old Tarahumara male was transferred from his community hospital with a 4-month history of cough, hemoptysis, progressive dyspnea, intermittent fever, and significant weight loss. On admission, he presented with a bad general condition, with the following vital signs: blood pressure of 90/60 mmHg, heart rate of 140 bpm, respiratory rate of 35 breaths per minute, and core body temperature of 99.5 F. The physical examination revealed a cachectic young man with evident signs of ARF including tachypnea, breathy speech, and accessory muscle use. Chest auscultation evidenced fine inspiratory crackles, mainly in the right apex. Arterial blood-gas (ABG) analysis while he breathed supplemental oxygen via a mask showed a pH of 7.37, PaO2 of 98 mmHg, PaCO2 of 36.5 mmHg, and HCO3 - of 20.8 mEq/L. Laboratory admission tests showed Hb of 11.1 g/dL, white blood count (WBC) of 11.6 cells/muL, neutrophils count of 10.9/muL, lymphocytes count of 0.2/muL, Na+ of 136 mmol/L, Cl- of 98 mmol/L, K+ of 4.02 mmol/L, Ca2+ of 7.6 mg/dL, glucose of 77 mg/dL, Cr of 0.36 mg/dL, blood urea nitrogen (BUN) of 6.1 mg/dL, uric acid of 3.7 mg/dL, cholesterol of 91 mg/dL, triglycerides of 98 mg/dL, and albumin of 2.1 g/dL. The HIV and hepatitis B and C tests were all negative. Sputum acid-fast stains were positive since his previous hospitalization and a real-time polymerase chain reaction (PCR) assay performed with another sputum sample confirmed the presence of Mycobacterium tuberculosis DNA. A chest X-ray showed diffuse alveolar and nodular opacities, as well an extensive right upper lobe cavitary disease (Figure 1). Based on the above findings, we calculated an APACHE II score of 13. The patient was treated with hydrocortisone 100 to 250 mg intravenously for 8 hours, and a daily regimen of intravenous amikacin 750 mg, and moxifloxacin 400 mg, along with antituberculosis treatment of 3 tablets of a fixed-dose combination (DoTBal, SILANES Laboratories) of rifampicin 150 mg, isoniazid 75 mg, pyrazinamide 400 mg, and ethambutol 300 mg. The patient was admitted to the intensive care unit but on day 4 in the hospital, the increased work of breathing required the initiation of NIPSV with a single-limb-circuit bilevel ventilator (VPAP III, ResMed) through an oronasal interface at pressures of 8-12/4 cm H2O. The DoTBal dose was increased to 4 tablets per day; however, the characteristic red color of the urine produced by rifampicin was no longer observed and the serum levels in a random sample were undetectable. Over the next 4 days despite slight improvement in PaCO2, it was not possible to wean the patient from NIPSV due to the persistent tachypnea. After a discussion regarding alternative therapies and under the respective observations of the local board of pharmacovigilance, the medical team decided as an extraordinary measure to administer etanercept (Enbrel, Wyeth Laboratories) 25 mg subcutaneously. The following day the patient showed a general improvement and an improved respiratory condition (Figure 2). After 2 days, he could finally be separated from NIPSV and undergo continued care in an isolated hospital ward breathing supplemental oxygen via nasal prongs. Three days after the first dose of etanercept, a second dose was administered without significant changes in the clinical condition of the patient. However, 4 days after the second dose of etanercept, the patient experienced exacerbation of respiratory symptoms, malaise, and fever of 100.5 F (Figure 2). Due to the short half-life of etanercept, this scenario was attributed to a paradoxical reaction and resolved promptly with the administration of a final third dose of etanercept along with hydrocortisone 200 mg intravenously. Within a few days, the clinical condition of the patient allowed his transfer to a unit with long-term care facilities, and after a month with negative smears for acid-fast bacilli he was finally discharged to their community under a directly observed therapy (DOT) program.