Mauricio Danckers

New drugs to treat multidrug-resistant tuberculosis: the case for bedaquiline

Mycobacterium tuberculosis develops spontaneous resistance mutants to virtually every drug in use. Courses of therapy select for these mutants and drug-resistant organisms emerge. The development of drug-resistant organisms has reached the point that drug resistance now threatens to undermine global success against tuberculosis (TB). New drugs are needed. The last new class of drugs specifically developed for treatment of TB was the rifamycins over 40 years ago. New funding sources and the development of product development partnerships have energized the TB drug development effort. There are now more TB drugs in development than at any time in the past. The first of these drugs to be developed and marketed was bedaquiline. Bedaquiline has an entirely novel mechanism of action and so should be active against otherwise highly resistant organisms. It acts on the transmembrane component of adenosine triphosphate synthase and acts by preventing electron transport. This raises the exciting possibility that bedaquiline may be active against less metabolically active organisms. Drug–drug interactions between rifamycins and the cytochrome P450-3A system will limit bedaquiline’s utility and create complexity in treatment regimens. In clinical trials, treatment with bedaquiline added to a background multidrug-resistant TB regimen was associated with earlier culture conversion and higher cure rates, but there were unexplained excess deaths in the bedaquiline arms of these trials. Food and Drug Administration approved bedaquiline for the treatment of multidrug-resistant TB when an effective treatment regimen cannot otherwise be provided. They required a black box warning about excess deaths and require that a phase III trial be completed. A planned Phase III trial is being reorganized. While bedaquiline is an exciting drug and marks a dramatic moment in the history of TB treatment, its ultimate place in the anti-TB drug armamentarium is unclear pending the Phase III trial and the development of other new drugs that are in the pipeline.

A Complication of Tracheobronchopathia Osteochondroplastica Presenting as Acute Hypercapnic Respiratory Failure

Patient: Male, 27 Final Diagnosis: Tracheobronchopathia osteochondroplastica Symptoms: Shortness of breath • stridor Medication: — Clinical Procedure: Neck computer tomography • pulmonary function test • neck surgical exploration • tracheostomy placement Specialty: Critical Care Medicine Objective: Unusual clinical course Background: Tracheobronchopathia osteochondroplastica is a rare benign and often indolent disease. We report the first case of tracheobronchopathia osteochondroplastica (TBO) presenting as acute hypercarbic respiratory failure due to superimposed subglottic submucosal abscess. Case Report: A 27-year-old man presented to the emergency department in respiratory distress that required mechanical ventilation for acute hypercarbic respiratory failure. Upon extubation the next day, stridor was elicited with ambulation. Spirometry revealed fixed upper airway obstruction. Neck imaging showed a 2.8×2.0×4.0 cm partially calcified subglottic mass with cystic and solid component obstructing 75% of the airway. Surgical exploration revealed purulent drainage upon elevation of the thyroid isthmus and an anterolateral cricoid wall defect in communication with a subglottic submucosal cavity. Microbiology was negative for bacteria or fungi. Pathology showed chondro-osseous metaplasia compatible with tracheobronchopathia osteochondroplastica (TBO). The patient received a course of antibiotics and prophylactic tracheostomy. Since tracheostomy removal 3 days later, the patient remains asymptomatic. Conclusions: Tracheobronchopathia osteochondroplastica is a rare disease with usually benign clinical course and incidental diagnosis. It may present as acute hypercarbic respiratory failure when subglottic infection is superimposed.

Black Pleural Effusion: A Unique Presentation of Metastatic Melanoma

Metastatic melanoma is a rare form of skin cancer, but one that comes with a high mortality rate. Pulmonary involvement is frequently seen in metastatic melanoma with only 2% of malignant melanoma patients with thorax metastasis presenting with pleural effusions. Herein, we report an extremely rare case of black pleural effusion from thoracic metastasis of cutaneous malignant melanoma. A 74-year-old man with known metastatic melanoma presented with a 1-month history of worsening lower back and hip pain and was found to have extensive osseous metastatic disease and multiple compression fractures. The patient underwent an uneventful kyphoplasty; however, the following day, he became acutely hypoxic and tachypneic with increased oxygen requirements. Radiographic evaluation revealed new bilateral pleural effusions. Bedside thoracentesis revealed a densely exudative, lymphocyte-predominant black effusion. Cytological examination showed numerous neoplastic cells with melanin deposition. A diagnosis of thoracic metastasis of malignant melanoma was established based on the gross and microscopic appearance of the pleural fluid. To the best of our knowledge, this is the first reported case of black pleural effusions secondary to metastatic melanoma in the United States. Despite the rarity of this presentation, it is important to determine the etiology of the black pleural effusion and to keep metastatic melanoma as a differential diagnosis.

Soft tissue laceration caused by lower extremity intraosseous access insertion in an obese patient

Intravenous access placement in the obese could be challenging due to unreliable anatomical landmarks and impact overall care. Intraosseous (IO) access remains a quick and reliable alternative to emergent intravenous access.1 2 The adult IO demonstrates an excellent safety profile with serious complications, such as compartment syndrome, osteomyelitis and skin abscesses, occurring in less than 1% of insertions.3 An 85-year-old woman presented with septic shock due to lobar pneumonia. Physical examination revealed a dehydrated, hypotensive, morbidly obese woman with anasarca and lower extremity lymphoedema. After several failed peripheral intravenous access attempts, IO access was achieved using the Arrow® …

Pulmonary metastasis in a patient with simultaneous bladder cancer and relapsing granulomatosis with polyangiitis.

Patient: Male, 70 Final Diagnosis: Metastatic micropapillary urothelial carcinoma Symptoms: Dry cough • dyspnea • hematuria Medication: Cyclophosphamide Clinical Procedure: Pulmonary wedge resection Specialty: Pulmonology Objective: Unusual clinical course Background: Granulomatosis with polyangiitis (GPA) relapse can complicate the differential diagnosis of pulmonary lesions. Case Report: A 70-year-old male smoker with GPA and emphysema presented with dyspnea, dry cough, and a right upper lobe pulmonary ground-glass opacity that persisted despite antibiotics. A trans-bronchial biopsy did not reveal active vasculitis, malignancy, or infection. He was treated for presumed GPA relapse based on pulmonary manifestations, renal failure, and elevated PR3-ANCA. Later, hematuria led to the cystoscopic discovery of a bladder wall lesion, which was diagnosed as micropapillary urothelial carcinoma not involving the muscularis propria. The patient developed an increasing pulmonary infiltrate with a new solid component, satellite lesions, and regional lymphadenopathy. A right upper lobe wedge resection showed metastatic urothelial carcinoma. Conclusions: The simultaneous presentation of a pulmonary lesion and GPA relapse is a diagnostic challenge. The differential diagnosis should include the rare possibility of metastatic urothelial carcinoma, regardless of how the lesion appears radiographically.

Duplicated Renal Collecting System

CLINICAL PRESENTATION A 27-year-old man with a history of chronic abdominal distention of unclear etiology presented with 1 week of fever, dysuria and increased abdominal girth. Examination revealed a distended, tender abdomen with shifting dullness and absence of the left testicle. A loculated fluid collection noted on abdominal ultrasound was sampled, suggesting bacterial peritonitis. Cultures from urine and ascitic fluid grew Enterococcus faecalis. Computed tomography of the abdomen (Figure 1) revealed a duplicated left kidney and collecting system with an obstructed upper pole moiety that inserted ectopically into the prostatic urethra. After completing a course of antibiotics, the patient underwent left percutaneous nephrostomy tube insertion. His follow-up computed tomography scan 8 weeks later (Figure 2) revealed decompression of the dilated collecting system and ureter. Presenting symptoms of ureteral anomalies are determined by the location of the distal urethral implantation site. Congenital giant megaureter may be associated with other genitourinary abnormalities, including cryptorchidism, duplex renal systems and megacalicosis. Our patient had all 3 of these associated findings. Abdominal masses or distension due to massive or cystic dilatation of the ureter are rare and present a challenge to clinical and radiological diagnosis. In our case, the patient underwent partial nephrectomy and uretherectomy, confirming the diagnosis of a congenital duplicated left kidney and collecting system. He remains well postoperatively.

Spontaneous coiling of a peripherally inserted central venous catheter

A 30-year-old man with extensively drug-resistant pulmonary tuberculosis and prior left upper lobe lobectomy presented to clinic for routine follow-up. His review of systems and physical examination were unremarkable. In addition to his oral antitubercular regimen, he was receiving intravenous capreomycin and meropenem through a right basilic vein single lumen peripherally inserted central catheter (PICC) placed 12 months prior. Routine chest X-ray (figure 1A), revealed a new PICC coiling (black arrow) within the right subclavian vein and migration of its distal end to the region of the brachiocephalic vein confluence. Contrast medium administered through the indwelling PICC (figure 1B) demonstrated …