Increased Moxifloxacin Dosing Among Patients With Multidrug-Resistant Tuberculosis With Low-Level Resistance to Moxifloxacin Did Not Improve Treatment Outcomes in a Tertiary Care Center in Mumbai, India.

BACKGROUND: Mycobacterium tuberculosis (Mtb) strains resistant to isoniazid and rifampin (multidrug-resistant tuberculosis [MDR-TB]) are increasingly reported worldwide, requiring renewed focus on the nuances of drug resistance. Patients with low-level moxifloxacin resistance may benefit from higher doses, but limited clinical data on this strategy are available. METHODS: We conducted a 5-year observational cohort study of MDR-TB patients at a tertiary care center in India. Participants with Mtb isolates resistant to isoniazid, rifampin, and moxifloxacin (at the 0.5 µg/mL threshold) were analyzed according to receipt of high-dose moxifloxacin (600 mg daily) as part of a susceptibility-guided treatment regimen. Univariable and multivariable Cox proportional hazard models assessed the relationship between high-dose moxifloxacin and unfavorable treatment outcomes. RESULTS: Of 354 participants with MDR-TB resistant to moxifloxacin, 291 (82.2%) received high-dose moxifloxacin. The majority experienced good treatment outcomes (200 [56.5%]), which was similar between groups (56.7% vs 54.0%, P = .74). Unfavorable outcomes were associated with greater extent of radiographic disease, lower initial body mass index, and concurrent treatment with fewer drugs with confirmed phenotypic susceptibility. Treatment with high-dose moxifloxacin was not associated with improved outcomes in either unadjusted (hazard ratio [HR], 1.2 [95% confidence interval {CI}, .6-2.4]) or adjusted (HR, 0.8 [95% CI, .5-1.4]) models but was associated with joint pain (HR, 3.2 [95% CI, 1.2-8.8]). CONCLUSIONS: In a large observational cohort, adding high-dose (600 mg) moxifloxacin to a drug susceptibility test-based treatment regimen for MDR-TB was associated with increased treatment-associated side effects without improving overall outcomes and should be avoided for empiric treatment of moxifloxacin-resistant MDR-TB.

Catastrophic costs of treating drug resistant TB patients in a tertiary care hospital in India.

BACKGROUND: Private healthcare is choice of point of care for 70% of Indians. Multidrug resistant tuberculosis (MDR-TB) treatment is costly and involves duration as long as 2 years. AIM: To estimate costs to patients undergoing treatment for MDR-TB. METHODS: A health-economics questionnaire was administered to 50 consecutive patients who successfully completed ambulatory private treatment for MDR-TB. Direct costs included drug costs, investigations, consultation fees, travel costs, hospitalisation and invasive procedures and cost prior to presentation to us. Indirect costs included loss of income. RESULTS: Of our cohort of 50 patients, 36 had pulmonary TB while 14 had extra-pulmonary TB (EPTB). 40 had MDR-TB and 10 had XDR-TB. There were 15 males and 35 females. Mean age was 30 years (range 16-61 years). Treatment cost for pulmonary MDR-TB averaged $5723 while it averaged $8401 for pulmonary XDR-TB and $5609 for EPTB. The major expense was due to drug costs (37%) while consultation fees were only 5%. Annual individual income for the cohort ranged from $0 to $63,000 (mean $11,430). On average, the cost of treatment ranged from 2.56% to 180.34% of the annual family income. 34/50 (68%) had total costs greater than 20% of annual family income and 39/50 (78%) had total costs greater than 10% of annual family income. The number of patients with total costs >40% of total family income was 22. CONCLUSION: MDR-TB in the private sector results in "catastrophic health costs". Financial and social support is essential for patients undergoing treatment for MDR-TB.

BCG and New Preventive Tuberculosis Vaccines: Implications for Healthcare Workers.

Healthcare workers (HCWs) are at high risk of Mycobacterium tuberculosis (Mtb) infection and tuberculosis disease, but also play a crucial role in implementing healthcare. Preexposure tuberculosis vaccination, including revaccination with BCG, might benefit Mtb-uninfected HCWs, but most HCWs in tuberculosis-endemic countries are already sensitized to mycobacteria. A new postexposure tuberculosis vaccine offers greatest potential for protection, in the setting of repeated occupational Mtb exposure. Novel strategies for induction of mycobacteria-specific resident memory T cells in the lung by aerosol administration, or induction of T cells with inherent propensity for residing in mucosal sites, such as CD1-restricted T cells and mucosa-associated innate T cells, should be explored. The need for improved protection of HCWs against tuberculosis disease is clear. However, health systems in tuberculosis-endemic countries would need significantly improved occupational health structures to implement a screening and vaccination strategy for HCWs.

Improved pulmonary function following pirfenidone treatment in a patient with progressive interstitial lung disease associated with systemic sclerosis.

Pirfenidone is an anti-fibrotic drug which has been approved for the management of patients with Idiopathic Pulmonary Fibrosis (IPF). However, its role in interstitial lung disease (ILD) due to other causes such as systemic sclerosis (SSc) is not clear. We present a case of a patient with SSc associated ILD who showed a subjective as well as objective improvement in lung function with pirfenidone.

Tropical pulmonary eosinophilia--a review.

Tropical pulmonary eosinophilia (TPE) is a syndrome of wheezing, fever and eosiniphilia seen predominantly in the Indian subcontinent and other tropical areas. Its etiological link with Wuchereria bancrofti and Brugia malayi has been well established. The pathogenesis is due to an exaggerated immune response to the filarial antigens which includes type I, type III and type IV reactions with eosinophils playing a pivotal role. Peripheral blood eosinophilia is usually striking with levels over 3000/µl being common. High serum levels of IgE and filarial-specific IgE and IgG are also found. The pathology may vary from an acute eosinophilic alveolitis to histiocytic infiltration depending on the stage of the disease. While earlier studies had suggested that the disease runs a benign course, more recent work has shown that untreated TPE could result in a fair degree of respiratory morbidity. Pulmonary function tests may show a mixed restrictive and obstructive abnormality with a reduction in diffusion capacity. The bronchoalveolar lavage (BAL) eosinophil count has a negative correlation with the diffusion capacity. Treatment consists of diethylcarbamazine (DEC) for at least three weeks. Despite treatment with DEC, about 20 per cent of patients may relapse. Steroids have shown to have a beneficial effect but the exact dose and duration is yet to be confirmed by randomized controlled trials. A specific and easily available marker is required for TPE in order to distinguish it from other parasitic and non-parasitic causes of pulmonary eosinophilia.

Fatal nitrofurantoin lung.

Nitrofurantoin is a drug commonly used for urinary tract infections. It acts by damaging bacterial DNA. It is given in dose of 50-100 mg orally and is generally considered a safe drug but has occasionally been known to cause pulmonary toxicity which is usually reversible and only rarely fatal. We present a case of an elderly lady receiving nitrofurantoin for her urinary tract infection who developed sudden acute lung injury to which she finally succumbed within a few weeks.