cAn effective regimen for treatment of tuberculosis (TB) is comprised of multiple drugs that inhibit a range of essential cellular activities in Mycobacterium tuberculosis. The effectiveness of a regimen is further enhanced if constituent drugs act with synergy. Here, we report that faropenem (a penem) or biapenem, doripenem, or meropenem (carbapenems), which belong to the -lactam class of antibiotics, and rifampin, one of the drugs that forms the backbone of TB treatment, act with synergy when combined. One of the reasons (carba)penems are seldom used for treatment of TB is the high dosage levels required, often at the therapeutic limits. The synergistic combination of rifampin and these (carba)penems indicates that (carba)penems can be administered at dosages that are therapeutically relevant. The combination of faropenem and rifampin also limits the frequency of resistant mutants, as we were unable to obtain spontaneous mutants in the presence of these two drugs. The combinations of rifampin and (carba)penems were effective not only against drug-sensitive Mycobacterium tuberculosis but also against drugresistant clinical isolates that are otherwise resistant to rifampin. A combination of doripenem or biapenem and rifampin also exhibited synergistic activity against Mycobacterium abscessus. Although the MICs of these three drugs alone against M. abscessus are too high to be of clinical relevance, their concentrations in combinations are therapeutically relevant; therefore, they warrant further evaluation for clinical utility to treat Mycobacterium abscessus infection, especially in cystic fibrosis patients.
BackgroundIndia with a major burden of multidrug-resistant tuberculosis (MDR-TB) does not have national level data on this hazardous disease. Since 2006, emergence of extensively drug-resistant TB (XDR-TB) is considered a serious threat to global TB control. This study highlights the demographic and clinical risk factors associated with XDR-TB in Delhi.MethodsThe study was conducted during April 2007 to May 2010. Six hundred eleven MDR-TB suspects were enrolled from four tertiary care hospitals, treating TB patients in Delhi and the demographic details recorded. Sputum samples were cultured using rapid, automated liquid culture system (MGIT 960). Drug susceptibility testing (DST) for Rifampicin (RIF) and Isoniazid (INH) was performed for all positive M. tuberculosis (M.tb) cultures. All MDR-TB isolates were tested for sensitivity to second-line drugs [Amikacin (AMK), Capreomycin (CAP), Ofloxacin (OFX), Ethionamide (ETA)].Results/FindingsOf 611, 483 patients were infected with MDR M. tuberculosis (M.tb) strains. Eighteen MDR-TB isolates (3.7%) were XDR M.tb strains. Family history of TB (p 0.045), socioeconomic status (p 0.013), concomitant illness (p 0.001) and previous intake of 2nd line injectable drugs (p 0.001) were significantly associated with occurrence of XDR-TB. Only two of the patients enrolled were HIV seropositive, but had a negative culture for M. tuberculosis. 56/483 isolates were pre-XDR M. tuberculosis, though the occurrence of pre-XDR-TB did not show any significant demographical associations.ConclusionsThe actual incidence and prevalence rate of XDR-TB in India is not available, although some scattered data is available. This study raises a concern about existence of XDR-TB in India, though small, signaling a need to strengthen the TB control program for early diagnosis of both tuberculosis and drug resistance in order to break the chains of transmission.
Presence of RVD in patients with a history of preexisting cardiac disease is an independent predictor of SCD irrespective of left ventricular ejection fraction.
Background Implantable loop recorders (ILRs) are effective in achieving symptom‐rhythm correlation. However, diagnostic yield in routine clinical practice is not well established. Methods Patients undergoing ILR implantation between April 2010 and May 2015 were included. All devices were enrolled in remote monitoring with automatic arrhythmia detection and P sense algorithms switched “ON.” Symptom‐rhythm correlation was assessed and changes in management were recorded. Results A total of 312 patients (57% male, age 53 ± 22 years; median CHADS2VaSc score = 1) were included in this study. ILRs were implanted for evaluation of syncope in 206 (66.0%), presyncope in 23 (7.4%), unexplained palpitations in 51 (16.3%), and cryptogenic stroke in 27 (8.7%) patients. ILR monitoring yielded a diagnosis that changed management strategy in 146 (46.8%) patients over a median of 12 (1‐42) months. Out of 163 (52.2%) patients with symptoms during the monitoring period, 100 (61.3%) had an arrhythmia. ILR was useful in ruling out an arrhythmic cause for symptoms in 63 (38.7%) patients. ILR results led to pacemaker implantation in 23 patients (7.4% overall and 11.2% of those with syncope) after median follow‐up of 3 months. A new diagnosis of atrial fibrillation was made in 38 (12.2%) patients, 11 of whom were initiated on oral anticoagulants. ILR results led to pacemaker implantation in 31 patients (9.9% overall and 19.0% of those with syncope) after median follow‐up of 3 months. A new diagnosis of atrial fibrillation was made in 38 (12.2%) patients, nine of whom were initiated on oral anticoagulants. Overall, ILR led to a change in management in 47% patients with a number needed to implant of 2.1 to change management. Conclusion ILR monitoring is effective in achieving symptom‐rhythm correlation and results in changes in management in nearly half of implanted patients. Additional studies are needed to evaluate cost efficacy of ILR and the optimal monitoring duration.
Allergic bronchopulmonary aspergillosis (ABPA) is an immunologically mediated disease characterized by a hypersensitivity reaction to fungal colonization by Aspergillus. Hydropneumothoraces and bronchopleural fistulae are rare occurrences in patients with ABPA. However, the diagnosis of ABPA is important to consider, as it is easily treatable with specific therapy. We report an unusual case of a patient with ABPA who presented to us with hydropneumothorax with bronchopleural fistula.
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