INTRODUCTION: Tuberculosis (TB) is still a serious public health problem in Los Angeles County, California. Approximately one-third of California's multi-drug-resistant (MDR) tuberculosis (TB) cases reside in Los Angeles County. MDR-TB is defined as TB resistant to at least both isoniazid (INH) and rifampin (RIF). The treatment of MDR-TB usually requires more toxic, less effective medications for a longer duration. Preventing transmission of MDR-TB is also critical. There has been less emphasis on universal access to laboratory techniques for the rapid diagnosis of TB and rapid drug susceptibility testing, which makes the management of MDR-TB a challenge.
CASE PRESENTATION: This case describes 32 year-old Asian male, who presented to the Los Angeles County + USC Medical Center emergency room with complains of shortness of breath, cough, fever, and night sweats for about a month. The patient did not have other known medical history or risk factor for MDR-TB, except for traveling frequently to Asia. His initial chest x-ray showed right upper lobe opacities. This presentation was suspicious for tuberculosis and he was initially empirically treated for TB with Rifampin, Isoniazid, Pyrazinamide, Ethambutol, as well as Ceftriaxone and Azithromycin for the possibility of community-acquired pneumonia. One day later, the sputum revealed 4+ acid-fast bacilli (AFB) and the serum tested positive for HIV. Despite three weeks of anti-tuberculosis therapy his chest x-rays showed worsening infiltrates and his oxygen requirements increased, so Trimethoprim/sulfamethoxale and Prednisone were initiated for possible Pneumocystis carinii co-infection. The possibility of MDR-TB was also considered. The explanation for clinical deterioration became obvious when the culture and sensitivity results became available thirty-seven days after they were collected. Mycobacterium tuberculosis was noted to be resistant to Isoniazid, Rifampin, Ethambutol, Streptomycin, Rifabutin, Azithromycin, and Clarythromycin. In response to these sensitivity results Isoniazid, Rifampin, and Ethambutol were discontinued, Pyrazinamide was continued, and six antibiotics were added: Moxifloxacin, Capreomycin, Cycloserine, Ethionamide, p-Aminosalicylic acid, and Linezolid. Highly active antiretroviral therapy was also initiated with Emtricitabine, Tenofovir, Lopinavir, and Ritonavir for further worsening in the patient's condition. His hospital course was further complicated by Linezolid related pancytopenia, depression and psychosis. After almost five months after admission, the patient's sputum stain is negative for AFB, but clinical epidemiologist recommended AFB negative cultures before permitting his discharge.
DISCUSSIONS: This case highlights the potential problem of MDR-TB to XDR-TB progression because of the difficulties to promptly diagnose and to effectively treat new cases of MDR-TB without early availability of rapid susceptibility testing information. Our patient has to wait more than 5 weeks to get the most optimal treatment for MDR-TB treatment. This case raises dual concern of potentially short-term ineffective therapy in a disease associated already with high risk for further morbidity and mortality, and the risk to develop further drug resistances if the case of TB isolates resistant to all first-line agents. In addition, there is a potential risk of spread of MDR-TB strain to healthcare workers because of a prolonged hospitalization and delayed diagnoses.
CONCLUSION: MDR-TB and XDR-TB are a global concerns associated with high morbidity and mortality. Rapid identification of drug susceptibilities is vitally important in cases of MDR-TB and XDR-TB. While universal access to rapid drug susceptibility methods is the ultimate goal, this reality is still far even in developed countries settings. New rapid diagnostic testing such as the Microscopic-Observation Drug-Susceptibility (MODS) assay and rapid molecular techniques are urgent priority in areas of the country were MDR-TB and XDR-TB can occur. In the meantime, physicians will repeatedly be challenged with difficult cases of potential MDR-TB infections and lack of availability of rapid diagnostic and susceptibility testing information.
DISCLOSURE: Ashish Patel, No Financial Disclosure Information; No Product/Research Disclosure Information