Limited information indicates that there are low levels of rifampin in breastmilk that would not be expected to cause any adverse effects in breastfed infants. The amount of rifampin in milk is insufficient to treat tuberculosis in the breastfed infant. The Centers for Disease Control and Prevention and other professional organizations state that breastfeeding should not be discouraged in women taking rifampin.[1-3] Breastmilk may be stained a yellow, orange, red or brown color.

Limited information indicates that maternal pyrazinamide therapy produces low levels in milk and would not usually be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months. Exclusively breastfed infants should be monitored for rare cases of jaundice, hepatitis and arthralgia if this drug is used during lactation.[1] The amount of pyrazinamide in milk is insufficient to treat tuberculosis in the breastfed infant. The Centers for Disease Control and Prevention and other professional organizations state that breastfeeding should not be discouraged in women taking pyrazinamide.[2-4]

The Centers for Disease Control and Prevention and other professional organizations state that breastfeeding should not be discouraged in women taking isoniazid. Nursing mothers who are taking isoniazid should take 25 mg of oral pyridoxine daily.[1,2] Because of the low levels of isoniazid in breastmilk and safe administration directly to infants, it is unlikely to cause adverse reactions in infants, but infants should be monitored for rare instances jaundice. Giving the maternal once-daily dose before the infant's longest sleep period will decrease the dose the infant receives. The amount of isoniazid in milk is insufficient to treat tuberculosis in the breastfed infant. If breastfed infants are treated with isoniazid, they should also receive pyridoxine 1 mg/kg daily.[3]

The activities of rifampin, nitazoxanide, PA-824, and sutezolid were tested against dormant Mycobacterium tuberculosis under conditions mimicking caseous granulomas (hypoxia at pH 7.3) in comparison with those of the combination rifampin-isoniazid-pyrazinamide-ethambutol (R-I-Z-E), which is used for human therapy. Mycobacterial viability was monitored by CFU and regrowth in MGIT 960. As shown by lack of regrowth in MGIT, rifampin-nitazoxanide-containing combinations, but not R-I-Z-E, killed dormant cells in 28 to 35 days. These observations might be important in designing new tuberculosis therapies.

Shorter duration of treatment for the management of drug-susceptible pulmonary tuberculosis (TB) would be a significant improvement in the care of patients suffering from the disease. Besides newer drugs and regimens, other modalities like host-directed therapy are also being suggested to reach this goal. This study's objective is to assess the efficacy and safety of metformin-containing anti-TB treatment (ATT) regimen in comparison to the standard 6-month ATT regimen in the treatment of patients with newly diagnosed sputum smear-positive drug-sensitive pulmonary TB.

The NiII complex 1 containing pyridyl- and hydroxy-functionalized N-heterocyclic carbenes (NHCs) is synthesized and its catalytic utility for the selective nitrile hydration to the corresponding amide under base-free conditions is evaluated. The title compound exploits a hemilabile pyridyl unit to interact with a catalytically relevant water molecule through hydrogen-bonding and promotes a nucleophilic water attack to the nitrile. A wide variety of nitriles is hydrated to the corresponding amides including the pharmaceutical drugs rufinamide, Rifater, and piracetam. Synthetically challenging α-hydroxyamides are accessed from cyanohydrins under neutral conditions. Related catalysts that lack the pyridyl unit (i.e., compounds 2 and 4) are not active whereas those containing both the pyridyl and the hydroxy or only the pyridyl pendant (i.e., compounds 1 and 3) show substantial activity. The linkage isomer 1' where the hydroxy group is bound to the metal instead of the pyridyl group was isolated under different crystallization conditions insinuating a ligand hemilabile behavior. Additional pKa measurements reveal an accessible pyridyl unit under the catalytic conditions. Kinetic studies support a ligand-promoted nucleophilic water addition to a metal-bound nitrile group. This work reports a Ni-based catalyst that exhibits functional hemilability for hydration chemistry.

A man aged 33 years, born in Nepal, but resident in the UK for 7 years presented to the emergency department with a 4-day history of general malaise, fever (temperature 38.6°C) and a non-productive cough. His medical history was unremarkable and no high-risk behaviour was identified. Clinical examination confirmed decreased air entry bilaterally with bibasal crackles. He was tachycardic, with a heart rate of 120 bpm. Further investigation with a 12-lead ECG confirmed supraventricular tachycardia (SVT) which was terminated with vagal manoeuvres. His chest radiograph demonstrated left basal consolidation. His white cell count was 11×109/L and his C reactive protein was 43.2 mg/L. His blood cultures revealed no growth. He was diagnosed with community-acquired pneumonia and started treatment with amoxicillin and clarithromycin. 3 days post admission, he was intubated for 24 hours in the Department of Intensive Care Medicine. Further episodes of SVT were observed and an ECHO showed a severely dilated and impaired left ventricle. Further chest radiographs illustrated diffuse consolidation with evidence of pulmonary oedema. HIV serology was negative. He developed transaminitis and thrombocytopenia. An ultrasound scan of his liver showed no obvious liver pathology. He remained tachypnoeic and due to worsening pulmonary oedema and extensive consolidation, he was readmitted to the intensive care unit. A CT abdomen with contrast showed an unusual pattern of lymphadenopathy with disproportionately enlarged coeliac axis nodes (5×7×5 cm) and minor para-aortic adenopathy, suspicious for lymphoma. On inserting his central venous catheter in his right internal jugular vein, pus was inadvertently aspirated from his right neck. Acid alcohol fast bacilli (AAFFB) were isolated from the pus and was subsequently identified as Mycobacterium tuberculosis He started treatment with antitubercular medication rifater: a combination of rifampicin 720 mg od, isoniazid 300 mg po od and pyrazinamide 1750 mg. In addition, he received ethambutol 1000 mg po od and pyridoxine 5 mg. He developed worsening metabolic acidosis, pH 7.19, loss of respiratory compensation and pancytopenia. Right heart strain was evident on his Focused Intensive Care Echo. He developed an increased oxygen requirement and respiratory distress on the ventilator. An erect chest radiograph showed bilateral pneumothoraces and bronchopleural fistulae. A chest drain was inserted. Following discussion with the Cardiothoracic Surgeons, pleurodesis was not deemed possible. He developed inotropic-dependent shock with worsening lung compliance. As a result of his deteriorating ventilation, acidosis and hyperkalaemia, he started treatment with continuous veno-venous haemofiltration. With a diagnosis of miliary tuberculosis and SVT causing cardiogenic pulmonary oedema, this man sadly died with his family at his bedside 10 weeks following initial hospital presentation.

Delamanid is a medicinal product approved for treatment of multidrug-resistant tuberculosis. Three studies were conducted to evaluate the potential drug-drug interactions between delamanid and antiretroviral drugs, including ritonavir, a strong inhibitor of CYP3A4, and selected anti-TB drugs, including rifampin, a strong inducer of cytochrome P450 (CYP) isozymes. Multiple-dose studies were conducted in parallel groups of healthy subjects. Plasma samples were analyzed for delamanid, delamanid metabolite, and coadministered drug concentrations, and pharmacokinetic (PK) parameters were determined. The magnitude of the interaction was assessed by the ratio of the geometric means and 90% confidence intervals. Coadministration of delamanid with tenofovir or efavirenz did not affect the PK characteristics of delamanid. Coadministration of Kaletra (lopinavir/ritonavir) with delamanid resulted in an approximately 25% higher delamanid area under the concentration-time curve from time 0 to the end of the dosing interval (AUCτ). Tenofovir, efavirenz, lopinavir, and ritonavir exposure were not affected by delamanid. Coadministration of delamanid with the TB drugs (ethambutol plus Rifater [rifampin, pyrazinamide, and isoniazid]) resulted in lower delamanid exposures (47 and 42% for the AUCτ and Cmax [maximum concentration of a drug in plasma] values, respectively), as well as decreased exposure of three primary metabolites (approximately 30 to 50% lower AUCτ values). Delamanid did not affect rifampin, pyrazinamide, and isoniazid exposure; the ethambutol AUCτ and Cmax values were about 25% higher with delamanid coadministration. The lack of clinically significant drug-drug interactions between delamanid and selected antiretroviral agents (including the strong CYP inhibitor ritonavir) and a combination of anti-TB drugs was demonstrated. Although there was a decrease in the delamanid concentrations when coadministered with ethambutol plus Rifater, this is likely related to decreased delamanid absorption and not to CYP induction.

Experimental and clinical studies have indicated that the antileprosy drug clofazimine may contribute treatment-shortening activity when included in tuberculosis treatment regimens. Clofazimine accumulates to high levels in tissues, has a long half-life, and remains in the body for months after administration is stopped. We hypothesized that in tuberculosis treatment, accumulated clofazimine may contribute sustained antimicrobial activity after treatment cessation, and we used the BALB/c mouse model of chronic tuberculosis chemotherapy to address this hypothesis. Mycobacterium tuberculosis-infected mice were treated for 4 weeks or 8 weeks with either isoniazid alone, clofazimine alone, the first-line regimen rifampin-isoniazid-pyrazinamide-ethambutol, or a first-line regimen where clofazimine was administered in place of ethambutol. To evaluate posttreatment antimicrobial activity, bacterial regrowth in the lungs and spleens was assessed at the day of treatment cessation and 2, 4, 6, and 8 weeks after treatment was stopped. Bacterial regrowth was delayed in all mice receiving clofazimine, either alone or in combination, compared to the mice that did not receive clofazimine. This effect was especially evident in mice receiving multidrug therapy. In mice not receiving clofazimine, bacterial regrowth began almost immediately after treatment was stopped, while in mice receiving clofazimine, bacterial regrowth was delayed for up to 6 weeks, with the duration of sustained antimicrobial activity being positively associated with the time that serum clofazimine levels remained at or above the 0.25-μg/ml MIC for M. tuberculosis Thus, sustained activity of clofazimine may be important in the treatment-shortening effect associated with this drug.

Rosacea is a common chronic inflammatory cutaneous disease of unknown etiology, characterized by remissions and exacerbations, presenting with centrofacial erythema and telangiectasias. It affects mainly adults around the age of 30 years and classically predominates in females. The pathophysiology of rosacea has not yet been fully understood. Risk factors are positive family history, very light skin phototype, sun exposure and consumption of spicy food or alcohol. Recently, there has been some evidence that some drugs or vitamins could be potential factors that can aggravate rosacea or induce rosacea-like symptoms. In this context, we present a 53-year-old female developing rosacea-like dermatitis due to a fixed combination of isoniazid and pyridoxine, which she was receiving along with rifampicin for the treatment of pulmonary tuberculosis.