Therapy For Pulmonary Tuberculosis Research Articles

Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment

Calcidiol, the major circulating metabolite of vitamin D, supports induction of pleiotropic antimicrobial responses in vitro. Vitamin D supplementation elevates circulating calcidiol concentrations, and thus has a potential role in the prevention and treatment of infection. The immunomodulatory effects of administering vitamin D to humans with an infectious disease have not previously been reported. To characterize these effects, we conducted a detailed longitudinal study of circulating and antigen-stimulated immune responses in ninety-five patients receiving antimicrobial therapy for pulmonary tuberculosis who were randomized to receive adjunctive high-dose vitamin D or placebo in a clinical trial, and who fulfilled criteria for per-protocol analysis. Vitamin D supplementation accelerated sputum smear conversion and enhanced treatment-induced resolution of lymphopaenia, monocytosis, hypercytokinaemia, and hyperchemokinaemia. Administration of vitamin D also suppressed antigen-stimulated proinflammatory cytokine responses, but attenuated the suppressive effect of antimicrobial therapy on antigen-stimulated secretion of IL-4, CC chemokine ligand 5, and IFN-α. We demonstrate a previously unappreciated role for vitamin D supplementation in accelerating resolution of inflammatory responses during tuberculosis treatment. Our findings suggest a potential role for adjunctive vitamin D supplementation in the treatment of pulmonary infections to accelerate resolution of inflammatory responses associated with increased risk of mortality.

Development and characterization of ligand-appended liposomes for multiple drug therapy for pulmonary tuberculosis

Tuberculosis (TB) remains one of the oldest and deadliest diseases in the current scenario. The intracellular organism Mycobacterium tuberculosis, which mainly resides in mononuclear phagocytes, is responsible for tuberculosis in humans. A few therapies are available for the treatment of tuberculosis but they have many hurdles. To overcome these hurdles, a combination of chemotherapeutic agent-loaded vesicular systems have been prepared to overcome tuberculosis. To investigate the role of novel drug delivery systems for the treatment of pulmonary tuberculosis, ligand appended liposomals have been developed. In the present study, drug-loaded, ligand-appended liposomes and their DPI (Dry Powder Inhaler) forms have been prepared and characterized using various in vitro and in vivo parameters. The prepared ligand-appended liposomal formulation showed good entrapment efficiency, prolonged drug release, improved recovery of drugs from the target site, and proved to be more suitable for use as DPI, justifying their potential for improved drug delivery. Thus we tried our best by our project to reduce the national burden of tuberculosis, which is still a global health challenge.

Durée de traitement des tuberculoses extrapulmonaires : six mois ou plus ? Analyse de la base de données TB-INFO

PurposeThe recommended duration of pulmonary tuberculosis therapy is 6months. For extrapulmonary tuberculosis, treatment duration depends on tuberculosis involvement and HIV status. The objective of this study was to describe the main characteristics of a cohort of extrapulmonary tuberculosis patients, to compare patients with a 6-month treatment to those with more than a 6-month treatment, and to analyze the compliance of medical centres with recommended duration of treatment. MethodsA retrospective cohort study of 210 patients with extrapulmonary tuberculosis was carried from January 1999 to December 2006 in two hospitals in the north-east of Paris. These patients were treated with quadruple therapy during two months, followed by dual therapy during 4months (n=77) or more (n=66). The characteristics of each group were compared by uni- and multivariate analysis. The primary endpoint was the rate of relapse or treatment failure at 24-month follow-up after treatment completion. ResultsNo relapse was observed after 24months of follow-up after the end of treatment in the two groups. In univariate analysis, patients with lymph node tuberculosis were more often treated for 6months than at other sites of tuberculosis (respectively 61% versus 40.9%; P=0.02); the decision of treatment duration was related to medical practices (79.2% treated 6months in one hospital versus 20.7% in the other, P<0.001); patients living in private residence were more often treated during 6months than patients living in residence (24.2% versus 10.3%, P=0.042). In multivariate analysis, only hospital (P=0.046), sex (P=0.007) and private residence were significantly different in each group. ConclusionA period of 6months seems to be sufficient to treat extrapulmonary tuberculosis (except for neuromeningeal localization).

Isoniazid preventive therapy and 4-year incidence of pulmonary tuberculosis among HIV-infected Thai patients

Human immunodeficiency virus (HIV) clinics at two Thai tertiary care medical centres. To evaluate the efficacy of tuberculin skin test (TST) guided isoniazid preventive therapy (IPT) in combination with antiretroviral therapy (ART) in the prevention of tuberculosis (TB). A 4-year prospective comparative study of patients at two HIV clinics: one performed TST at enrolment and, if positive, prescribed IPT (IPT group), while the other did not perform TST (non-IPT group). There were 200 patients included in each group. Baseline characteristics and drop-out rates were similar in both groups. The incidence of pulmonary TB over 4 years was not significantly different between the IPT and non-IPT groups (0.80 cases vs. 1.76 per 100 person-years [py], P = 0.13). However, the incidence of pulmonary TB in the non-IPT group was significantly higher during the first 6 months (8.60 vs. 0 cases/100 py, P = 0.01) and among patients with initial CD4 < 200 cells/l (9.41 vs. 0 cases/100 py, P = 0.02). The survival analyses demonstrated a protective effect of IPT (x(2) = 3.66, P = 0.04) for early TB. Benefit of IPT plus ART was evident only in the first 6 months of care. These findings suggest that TST-guided IPT should be routinely provided for HIV-infected patients after initial entry into medical care.

Biomarkers of Oxidative Stress and Personalized Treatment of Pulmonary Tuberculosis: Emerging Role of Gamma-Glutamyltransferase

Background. The objectives were (i) to evaluate the impact of acute pulmonary tuberculosis (PTB) and anti-TB therapy on the relationship between AST, ALT, and GGT levels in absence of conditions related to hepatotoxicity; (ii) to evaluate the rate and the time of alterations of AST, ALT, and GGT. Design and Methods. A prospective followup of 40 adults (21 males; mean age of 34.7 ± 5.8 years) with active PTB on initial phase and continuation phase anti-TB. Results. Only 3% (n = 1) developed a transient and benign ADR at day 30 without interruption of anti-TB treatment. Within normal ranges, GGT decreased significantly from day 0 to day 60, while AST and ALT increased significantly and respectively. During day 0–day 60, there was a significant, negative, and independent association between GGT and AST. Conclusion. The initial two months led to significant improvement of oxidative stress. Values of oxidative markers in normal ranges might predict low rate of ADR.

A Case of Stevens-Johnson Syndrome (SJS) Progressive Toxic Epidermal Necrolysis (TEN) Onset During Hyposensitization Therapy for Pulmonary Tuberculosis Complicated with Dermatomyositis

A 58-year-old female with a history of dermatomyositis was receiving large oral doses of steroids. She had pulmonary tuberculosis and developed a fever, systemic exudative erythema, exanthema, and epidermolysis covering 30% of her body surface area while being treated with four agents, including isoniazid (INH) and rifampicin (RFP). Histopathologically, eosinophilic necrosis was observed in all layers of the epidermis and a diagnosis of Stevens-Johnson syndrome (SJS) progressive toxic epidermal necrolysis (TEN) was made. The drugs suspected in the drug-induced lymphocyte stimulation test (DLST) re-testing were INH and RFP, and the DLST was considered to be important during the recovery period as well as in the acute phase. Early treatment with plasma exchange therapy and large quantities of intravenous immunoglobulin (IVIG) was successful. Plasma exchange therapy and IVIG are extremely effective when SJS and TEN occur in a patient already on high-dose steroid therapy. Note that the incidence of SJS and TEN is believed to be higher in patients with collagen disease, such as in our case, as compared to the general population.

Opportunistic microorganisms in patients undergoing antibiotic therapy for pulmonary tuberculosis

Antimicrobial therapy may cause changes in the resident oral microbiota, with the increase of opportunistic pathogens. The aim of this study was to compare the prevalence of Candida, Staphylococcus, Pseudomonas and Enterobacteriaceae in the oral cavity of fifty patients undergoing antibiotic therapy for pulmonary tuberculosis and systemically healthy controls. Oral rinsing and subgingival samples were obtained, plated in Sabouraud dextrose agar with chloramphenicol, mannitol agar and MacConkey agar, and incubated for 48 h at 37°C. Candida spp. and coagulase-positive staphylococci were identified by phenotypic tests, C. dubliniensis, by multiplex PCR, and coagulase-negative staphylococci, Enterobacteriaceae and Pseudomonas spp., by the API systems. The number of Candida spp. was significantly higher in tuberculosis patients, and C. albicans was the most prevalent specie. No significant differences in the prevalence of other microorganisms were observed. In conclusion, the antimicrobial therapy for pulmonary tuberculosis induced significant increase only in the amounts of Candida spp.

Pilot Study of Twice-weekly Therapy for Pulmonary Tuberculosis in Taiwan

Taiwan has never implemented supervised intermittent chemotherapy for pulmonary tuberculosis, and its application and results are unknown. The purpose of this study was to evaluate the efficacy and feasibility of a 62-dose, four-drug, 6-month, twice-weekly regimen administered by directly observed therapy for the treatment of pulmonary tuberculosis. From January 2004 through December 2006, a total of 116 patients with suspected or confirmed pulmonary tuberculosis were enrolled. Thirty-two of these patients were excluded from the analysis because of drug resistance, negative culture, self withdrawal and drug reactions. Isoniazid, rifampin, pyrazinamide, and ethambutol were administered daily for 2 weeks, followed by twice weekly at a higher dose for 6 weeks. Thereafter, isoniazid, ethambutol and rifampin were administered twice weekly for 18 weeks. Treatment was directly observed by nurses or outreach workers. Of the 84 evaluable patients, 75 [89.3%, 95% confidence interval (CI): 80.6s-95.0%] patients were considered as successfully treated, three (3.6%, 95% CI: 0.7-10.1%) transferred out, five (6.0%, 95% CI: 2.0-13.3%) were unsuccessful and one (1.2%, 95% CI: 0.03-6.5%) died. Five patients were treatment failure (6.0%, 95% CI: 2.0-13.3%). Three patients had recurrences of pulmonary tuberculosis, and the recurrences were 4, 6 and 15 months after the completion of therapy. Sixpatients (5.2%) had severe adverse drug reactions and had their regimen modified. Prior to this study, intermittent therapy has not been attempted in Taiwan. This four-drug mostly twice-weeldy pulmonary tuberculosis treatment regimen is efficacious and relatively nontoxic, with a higher treatment success rate and a lower death rate. It considerably simplifies treatment and facilitates the execution of directly observed therapy. The reasons for the relatively high failure rate require further studies.

Return of the usual suspect

In October, 2010, a 76-year-old woman born in the USA presented to our emergency department complaining of a severe sore throat and painful swallowing. She reported having had a non-productive cough without haemoptysis 1 month previously. The cough resolved, but a sore throat then developed. At the time she was assessed by her general practitioner and specialists in the emergency and otolaryngology departments, who diagnosed pharyngitis and recommended conservative management. Her odynophagia progressed until she was unable to eat solid foods, prompting her to present to our hospital. She denied fevers, chills, night sweats, myalgias, dysphonia, dyspnoea, or dysphagia but did report a 7 kg weight loss. She also reported occasional tobacco and alcohol use. On examination she was afebrile and thin but appeared well. She had dry mucous membranes and mild erythema of the posterior pharynx without tonsilar enlargement or exudate. No oral thrush, cervical lymphadenopathy, rales, splenomegaly, or rash were noted. Leucocyte concentration was 7·9 × 109/L with a predominance of neutrophils. She was admitted for further assessment. Rapid streptococcal antigen test, monospot test, human immunodefi ciency virus (HIV) antibody test, and rapid antigen test for infl uenza A and B were negative. A temperature of 38·7°C prompted a chest radiograph, which showed bilateral airspace disease and an area of dense consolidation in the right upper lung with a rounded lucency likely to be cavitation (fi gure A), subsequently confi rmed on chest CT (fi gure B). CT of her neck showed non-specifi c epiglottis oedema. Purifi ed protein derivative skin test was negative. A few acid fast bacilli were present in the sputum, and she was started on empiric therapy for presumed pulmonary tuberculosis. DNA probe performed on sputum confi rmed Mycobacterium tuberculosis which was sensitive to all antituberculous drugs tested. Subsequently, her fever and odynophagia resolved. Laryngeal tuberculosis was the most likely cause of our patient’s sore throat as evidenced by her clinical symptoms and presumed active pulmonary tuberculosis, the non-specifi c oedema of the epiglottis noted on CT, and the resolution of her sore throat and odynophagia with antituberculous therapy. However, a defi nitive diagnosis cannot be made without laryngoscopy and histopathological confi rmation; laryngoscopy was deferred because of the substantial infectious risk associated with the procedure in the setting of active tuberculosis. She was discharged with instructions for tuberculosis testing of close contacts and plans for direct observed therapy. At last contact in February, 2011, she was well, with no recurrence of symptoms. Laryngeal tuberculosis, which accounted for 25% of all cases of tuberculosis in the early 20th century, now accounts for less than 1% of cases and is typically associated with pulmonary infection. Whereas extrapulmonary tuberculosis occurs frequently in persons with HIV, cases of laryngeal tuberculosis have been reported in immunocompetent persons. Our patient presented with odynophagia, a common presenting complaint in patients with laryngeal tuberculosis, but she denied hoarseness, the most common presenting symptom. She denied any history of tuberculosis or known contact with persons with tuberculosis, but she did report having worked as a home health aide during the 1970s. Laryngeal tuberculosis results from either direct bronchogenic spread from infected sputum or, less commonly, haematogenous spread. Laryngeal tuberculosis is highly infectious, and a delay in diagnosis can lead to disease progression and longer exposure to contacts. Therefore, physicians should consider laryngeal tuberculosis in the diff erential diagnosis of patients presenting with a persistent sore throat and odynophagia, especially in patients such as ours who also report weight loss. A chest radiograph should be considered before laryngoscopy to minimise unnecessary risk to healthcare providers.

Home oxygen therapy in pulmonary tuberculosis and pulmonary atypical mycobacteriosis during chemotherapy

During the period of eight years from 1985 to 1992 we had sixteen patients (pulmonary tuberculosis: 6, atypical mycobacteriosis: 10) who had been under the treatment for tuberculosis and on whom home oxygen therapy (HOT) was started. Of sixteen patients twelve had history of antituberculous therapy in the past. There were nine chronic active or persistently sputum positive patients of whom three were pulmonary tuberculosis and six atypical mycobacteriosis. The duration of illness was long in these patients and it was more than ten years in tuberculosis patients. Four cases died, two cases of pulmonary tuberculosis died from hemoptysis, and two cases of atypical mycobacteriosis died from respiratory failure.

Mathematical modeling of pulmonary tuberculosis therapy: Insights from a prototype model with rifampin

There is a critical need for improved and shorter tuberculosis (TB) treatment. Current in vitro models of TB, while valuable, are poor predictors of the antibacterial effect of drugs in vivo. Mathematical models may be useful to overcome the limitations of traditional approaches in TB research. The objective of this study was to set up a prototype mathematical model of TB treatment by rifampin, based on pharmacokinetic, pharmacodynamic and disease submodels. The full mathematical model can simulate the time-course of tuberculous disease from the first day of infection to the last day of therapy. Therapeutic simulations were performed with the full model to study the antibacterial effect of various dosage regimens of rifampin in lungs. The model reproduced some qualitative and quantitative properties of the bactericidal activity of rifampin observed in clinical data. The kill curves simulated with the model showed a typical biphasic decline in the number of extracellular bacteria consistent with observations in TB patients. Simulations performed with more simple pharmacokinetic/pharmacodynamic models indicated a possible role of a protected intracellular bacterial compartment in such a biphasic decline. This modeling effort strongly suggests that current dosage regimens of RIF may be further optimized. In addition, it suggests a new hypothesis for bacterial persistence during TB treatment.

Opportunistic microorganisms in patients undergoing antibiotic therapy for pulmonary tuberculosis

Antimicrobial therapy may cause changes in the resident oral microbiota, with the increase of opportunistic pathogens. The aim of this study was to compare the prevalence of Candida, Staphylococcus, Pseudomonas and Enterobacteriaceae in the oral cavity of fifty patients undergoing antibiotic therapy for pulmonary tuberculosis and systemically healthy controls. Oral rinsing and subgingival samples were obtained, plated in Sabouraud dextrose agar with chloramphenicol, mannitol agar and MacConkey agar, and incubated for 48 h at 37°C. Candida spp. and coagulase-positive staphylococci were identified by phenotypic tests, C. dubliniensis, by multiplex PCR, and coagulase-negative staphylococci, Enterobacteriaceae and Pseudomonas spp., by the API systems. The number of Candida spp. was significantly higher in tuberculosis patients, and C. albicans was the most prevalent specie. No significant differences in the prevalence of other microorganisms were observed. In conclusion, the antimicrobial therapy for pulmonary tuberculosis induced significant increase only in the amounts of Candida spp.

Activity of Pyrazinamide in the Guinea Pig Model of Tuberculosis

Ordway et al. (8) have recently evaluated standard chemotherapy with a combination of rifampin, isoniazid, and pyrazinamide (PZA) in the guinea pig model of tuberculosis (TB) and described long-term bacterial persistence. Soon after the introduction of PZA in 1952, perhaps the most experienced group examining the activity of antituberculosis drugs in the guinea pig model reported that PZA had little or no activity (9). In the two guinea pig experiments they describe, established tuberculosis was treated, starting 21 or 30 days after infection with strain H37Rv, with about 150 mg PZA/kg of body weight twice daily by gavage for periods of 75 or 100 days. Deaths occurred in 3 of 22 untreated control animals and in 5 of 20 PZA-treated animals, with total organ macroscopic scores of 10.8 and 13.5 (controls) and 9.2 and 9.6 (PZA), while a group treated with isoniazid (5 mg/kg/day) intramuscularly (i.m.) had no deaths and a score of 3.5. From a search of the literature, no one has apparently reported similar observations in the guinea pig model using more modern methods of assessment. While PZA had such low activity in the guinea pig, it is almost as active in human lesions as rifampin. PZA and rifampin are together responsible for almost all of the sterilizing activity of the standard treatment of pulmonary tuberculosis (1, 7). PZA has high activity against persisters, particularly those that are rifampin tolerant (4). Clearly, valid assessments cannot be made of current standard therapy in pulmonary tuberculosis using the guinea pig model unless it can be shown that PZA has similar activities in both. It could be argued that PZA might be more active in combination than when given alone, so an assessment of its efficacy in monotherapy could be misleading. However, in the mouse model, treatment with PZA alone was highly bactericidal, although eventually limited by the emergence of resistance, and is equally active in combined treatment (2). In pulmonary TB, PZA given alone for the first 14 days was highly bactericidal (5). Thus, available evidence suggests that a good model for human combined treatment should show PZA to be demonstrably active both given alone and in combination. Human pulmonary lesions are thought to have a pH slightly on the acidic side, estimated between pH 5.5 and pH 6.0 (3, 6). Could inactivity in the guinea pig be due to lower acidity in the lesions because their degree of hypersensitivity to tuberculins is less than that in humans?

Usefulness of 18F-FDG positron emission tomography/computed tomography for the diagnosis of pyothorax-associated lymphoma: A report of three cases

Pyothorax-associated lymphoma (PAL) is a unique and rare non-Hodgkin's lymphoma developing in the pleural cavity following a long-standing history of chronic pyothorax (CP). The development of F-18 2'-deoxy-2fluoro-D-glucose (FDG) positron emission tomography combined with computed tomography (PET/CT) has contributed to the evaluation of lymphoma staging. However, only a few studies describing FDG-PET/CT findings in PAL have been published. This study reported three cases of PAL; all 3 patients had previously undergone artificial collapse therapy for pulmonary tuberculosis. Both the first case (an 84-year-old male) and second case (an 83-year-old male) complained of abdominal pain. An ultrasound scan revealed a mass shadow in the left chest wall without abnormal findings in the abdomen, and the CT and magnetic resonance imaging scans suggested malignant lymphoma of the left chest. FDG-PET/CT imaging showed extremely intense FDG uptake only in the left pleura and chest wall. Diagnosis was CP in the two patients, showing a high maximum standardized uptake value (SUVmax: early, 14.8 and delayed, 19.4 in the first case; early, 20.8 and delayed, 27.3 in the second case, respectively). Histopathological analysis of the specimens obtained by biopsy of the PET/CT-positive pleural mass showed non-Hodgkin's, diffuse large B cell lymphoma in the two cases. The third case was a 79-year-old male with relapse after right pleuropneumonectomy for PAL (diffuse large B cell lymphoma) 4 years earlier. PET/CT showed intense FDG uptake (SUVmax: early, 19.9 and delayed, 35.7) in the right pleura and chest wall. Diagnosis was CP, suggesting the recurrence of PAL. Furthermore, abnormal intense FDG uptake was noted in the hilar, mediastinal and supraclavicular lymph nodes, as well as in the spleen. In conclusion, FDG-PET/CT imaging is useful in the evaluation of the area of invasion in PAL.

In vitro evaluation of inhalable isoniazid‐loaded surfactant liposomes as an adjunct therapy in pulmonary tuberculosis

In this study, exogenous pulmonary surfactant was evaluated as an inhalable drug carrier for antitubercular drug isoniazid (INH). Isoniazid-entrapped liposomes of dipalmitoylphosphatidylcholine (DPPC) (the most abundant lipid of lung surfactant and exogenous surfactant) were developed and evaluated for size, drug entrapment, release, in vitro alveolar deposition, biocompatibility, antimycobacterial activity, and pulmonary surfactant action. Isoniazid-entrapped DPPC liposomes were about 750 nm in diameter and had entrapment efficiency of 36.7% +/- 1.8%. Sustained release of INH from DPPC liposomes was observed over 24 h. In vitro alveolar deposition efficiency using the twin impinger exhibited approximately 25-27% INH deposition in the alveolar chamber upon one minute nebulization using a jet nebulizer. At 37 degrees C, the formulation had better pulmonary surfactant function with quicker reduction of surface tension on adsorption (36.7 +/- 0.4 mN/m) than DPPC liposomes (44.7 +/- 0.6 mN/m) and 87% airway patency was exhibited by the formulation in a capillary surfactometer. The formulation was biocompatible and had antimycobacterial activity. The isoniazid-entrapped DPPC liposomes could fulfill the dual purpose of pulmonary drug delivery and alveolar stabilization due to antiatelectatic effect of the surfactant action which can improve the reach of antitubercular drug INH to the alveoli.

Brief history of the development of artificial pneumothorax

Artificial pneumothorax (AP), was one kind of surgery for pulmonary tuberculosis which injects the air into the pleural cavity by needle tubes to form the artificial pneumothorax. It was applied in a clinic by the Italian physician Carlo Forlanini in 1894. In the subsequent 20 years, this therapy has not been paid attention to in medical circles until 1912 when it received recognition and gradually became the primary therapy of pulmonary tuberculosis in Europe and America. AP began to be used in pulmonary tuberculosis from 1928 to 1930 in Shanghai, China, then throughout the whole country. In the 1950s, with the appearance of streptomycin, streptomycin and rifampicin, AP gradually withdrew from the front-line of clinical practice and became a thing of the past.

Immunomodulation with Recombinant Interferon-γ1b in Pulmonary Tuberculosis

BackgroundCurrent treatment regimens for pulmonary tuberculosis require at least 6 months of therapy. Immune adjuvant therapy with recombinant interferon-γ1b (rIFN-γb) may reduce pulmonary inflammation and reduce the period of infectivity by promoting earlier sputum clearance.Methodology/Principal FindingsWe performed a randomized, controlled clinical trial of directly observed therapy (DOTS) versus DOTS supplemented with nebulized or subcutaneously administered rIFN-γ1b over 4 months to 89 patients with cavitary pulmonary tuberculosis. Bronchoalveolar lavage (BAL) and blood were sampled at 0 and 4 months. There was a significant decline in levels of inflammatory cytokines IL-1β, IL-6, IL-8, and IL-10 in 24-hour BAL supernatants only in the nebulized rIFN-γ1b group from baseline to week 16. Both rIFN-γ1b groups showed significant 3-fold increases in CD4+ lymphocyte response to PPD at 4 weeks. There was a significant (p = 0.03) difference in the rate of clearance of Mtb from the sputum smear at 4 weeks for the nebulized rIFN-γ1b adjuvant group compared to DOTS or DOTS with subcutaneous rIFN-γ1b. In addition, there was significant reduction in the prevalence of fever, wheeze, and night sweats at 4 weeks among patients receiving rFN-γ1b versus DOTS alone.ConclusionRecombinant interferon-γ1b adjuvant therapy plus DOTS in cavitary pulmonary tuberculosis can reduce inflammatory cytokines at the site of disease, improve clearance of Mtb from the sputum, and improve constitutional symptoms.Trial RegistrationClinicalTrials.gov NCT00201123

Nontuberculous mycobacteria isolated during the treatment of pulmonary tuberculosis

The significance of nontuberculous mycobacteria (NTM) isolated from a patient during therapy for pulmonary tuberculosis (TB) is uncertain. We investigated the frequency and clinical significance of NTM isolated from patients receiving anti-TB treatment. We conducted a retrospective cohort study of all patients with culture-confirmed pulmonary TB, and identified patients with respiratory cultures positive for NTM during therapy for pulmonary TB. From January 2003 to December 2005, 958 patients were diagnosed with culture-confirmed pulmonary TB. NTM were isolated from 113 specimens in 68 (7.1%) patients during anti-TB treatment. The most frequently isolated NTM species were Mycobacterium abscessus (n=35, 31%), Mycobacterium fortuitum (n=17, 15%), Mycobacterium avium complex (n=9, 8%), and Mycobacterium gordonae (n=9, 8%). Forty-eight (71%) patients had only one positive culture, while 20 (29%) had two or more positive cultures for NTM. Only two (3%) patients who had two or more positive culture after anti-TB treatment showed the same NTM species, which were M. abscessus. The isolation of NTM in patients with pulmonary TB is not uncommon during anti-TB treatment. However, this is likely the result of colonization, a transient infection, or specimen contamination. The co-existence of pulmonary TB and NTM lung disease may be rare but should be considered in patients with relatively virulent NTM species such as M. abscessus.

Vitamin D as Adjunctive Therapy in Refractory Pulmonary Tuberculosis: A Case Report

Vitamin D regulates calcium homeostasis in the body and may play a major role in regulating immune responses to tuberculosis (TB). Pilot studies suggest that vitamin D supplementation may improve outcomes in pulmonary TB (PTB), but clinical evidence using vitamin D in TB treatment is limited. We present a case of vitamin D deficiency in a woman with refractory drug-susceptible PTB. Antituberculous therapy and the correction of vitamin D deficiency resulted in clinical and microbiologic improvement at month 13 of her treatment. The basis for vitamin D/TB interactions and a brief literature review are discussed. Data from controlled trials are needed to evaluate the efficacy of vitamin D as adjunctive TB therapy.

Bactericidal Activity of Moxifloxacin on Exponential and Stationary Phase Cultures of Mycobacterium tuberculosis

The bactericidal activity of moxifloxacin, alone and in combination with isoniazid and rifampin, was studied on exponential and stationary phase cultures of Mycobacterium tuberculosis H37 Rv strain, the standard strain which is a wild type of M. tuberculosis strain, not exposed to any environment, susceptible to all anti-tuberculosis drugs. moxifloxacin alone was highly bactericidal, being intermediate in activity between isoniazid and rifampin on both types of culture. the speed of activity was slow with the stationary phase culture, causing a reduction from 6.41 log10 cfu/ml to 2.70 log10 cfu/ml on day 6 with the higher moxifloxacin concentration of 4 μg/ml and to 4.08 log10 cfu/ml with the lower concentration of 0.25 μg/ml. when added to isoniazid, its activity against both exponential and stationary phase cultures was increased. However, when it was added to rifampin, no increase in activity was found with either type of culture. Addition of moxifloxacin to isoniazid and rifampin resulted in a slight increase in activity against the exponential culture but a considerable increase against the stationary culture with counts below the limit of detection at 4 and 6 days with both moxifloxacin concentrations. The synergism found with isoniazid, but not with rifampin, supports the view that isoniazid should be included in combinations with moxifloxacin during the therapy of pulmonary tuberculosis.