- Repositioning rifamycins for Mycobacterium abscessus lung disease. [Journal Article]
- EOExpert Opin Drug Discov 2019 Jun 14; :1-12
- Introduction: The treatment of Mycobacterium abscessus lung disease faces significant challenges due to intrinsic antibiotic resistance. New drugs are needed to cure this incurable disease. The key a…
Introduction: The treatment of Mycobacterium abscessus lung disease faces significant challenges due to intrinsic antibiotic resistance. New drugs are needed to cure this incurable disease. The key anti-tubercular rifamycin, rifampicin, suffers from low potency against M. abscessus and is not used clinically. Recently, another member of the rifamycin class, rifabutin, was shown to be active against the opportunistic pathogen. Areas covered: In this review, the authors discuss the rifamycins as a reemerging drug class for treating M. abscessus infections. The authors focus on the differential potency of rifampicin and rifabutin against M. abscessus in the context of intrinsic antibiotic resistance and bacterial uptake and metabolism. Reports of rifamycin-based drug synergies and rifamycin potentiation by host-directed therapy are evaluated. Expert opinion: While repurposing rifabutin for M. abscessus lung disease may provide some immediate relief, the repositioning (chemical optimization) of rifamycins offers long-term potential for improving clinical outcomes. Repositioning will require a multifaceted approach involving renewed screening of rifamycin libraries, medicinal chemistry to improve 'bacterial cell pharmacokinetics', better models of bacterial pathophysiology and infection, and harnessing of drug synergies and host-directed therapy towards the development of a better drug regimen.
- Cost of managing severe cutaneous adverse drug reactions to first-line tuberculosis therapy in South Africa. [Journal Article]
- TMTrop Med Int Health 2019 Jun 07
- CONCLUSIONS: CADR to anti-tuberculosis treatment represent a significant economic burden. An alternate strategy of outpatient-initiated second-line therapy is economically feasible but requires clinical validation to assess effectiveness. This article is protected by copyright. All rights reserved.
- Safety and efficacy of rifabutin among HIV/TB-coinfected children on lopinavir/ritonavir-based ART. [Journal Article]
- JAJ Antimicrob Chemother 2019 May 28
- CONCLUSIONS: With clinical and laboratory monitoring, our data suggest that rifabutin is a safe option for TB therapy among children on PI-based ART. By contrast with the only other study of this combination in children, severe neutropenia was rare. Furthermore, outcomes from this cohort suggest that rifabutin is effective, and a novel option for children who require PI-based ART. Additional study of rifabutin plus PIs in children is urgently needed.
- Resolution of a Localized Granuloma Caused by Mycobacterium avium-intracellulare Complex on the Cere of a Bruce's Green Pigeon (Treron waalia). [Journal Article]
- JAJ Avian Med Surg 2018; 32(4):322-327
- A 3-year-old female Bruce's green pigeon (Treron waalia) was presented with granulomatous inflammation of the cere and underlying tissues with osteomyelitis and bone proliferation of the dorsal prema…
A 3-year-old female Bruce's green pigeon (Treron waalia) was presented with granulomatous inflammation of the cere and underlying tissues with osteomyelitis and bone proliferation of the dorsal premaxilla. Biopsy and culture revealed the presence of Mycobacterium avium-intracellulare complex, and multi-antimicrobial treatment was initiated with clarithromycin, ethambutol, rifabutin, and enrofloxacin. The cere lesion improved and no evidence of systemic granulomas was observed over 4 months of treatment, although leukocytosis and monocytosis persisted. Five months after discontinuation of antibiotic therapy, the white blood cell count had normalized, but distal beak irregularities and partial recurrence of the mass were present. The bird died 15 months after discontinuation of antibiotic therapy and necropsy revealed no evidence of active mycobacteriosis of the beak or cere. This report documents an unusual clinical presentation of mycobacteriosis, in addition to its successful resolution.
- Tuberculosis. [Review]
- NCNurs Clin North Am 2019; 54(2):193-205
- Drug-resistant tuberculosis (TB) is one of the greatest challenges facing the elimination of TB. In the United States, persons born outside the United States account for 70% of new TB cases. Nucleic …
Drug-resistant tuberculosis (TB) is one of the greatest challenges facing the elimination of TB. In the United States, persons born outside the United States account for 70% of new TB cases. Nucleic acid amplification testing has greatly reduced the amount of time needed for diagnosis of TB, down to 1 to 2 days, compared with waiting 21 days for culture results. The shorter treatment regimen for latent TB infection with weekly isoniazid and rifabutin for 12 weeks provides treatment as effective as the traditional daily isoniazid for 6 months, but with better adherence from patients.
- rpoB Mutations Causing Discordant Rifampicin Susceptibility in Mycobacterium tuberculosis: Retrospective Analysis of Prevalence, Phenotypic, Genotypic, and Treatment Outcomes. [Journal Article]
- OFOpen Forum Infect Dis 2019; 6(4):ofz065
- CONCLUSIONS: Rifampicin-discordant TB is not uncommon and sequencing is required to confirm results. The high susceptibility to rifabutin and isoniazid and poor treatment outcomes with the current regimen suggest a potential utility for rifabutin-based therapy.
- Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome caused by first-line antituberculosis drugs: Two case reports and a review of the literature. [Journal Article]
- CDContact Dermatitis 2019 Apr 25
- CONCLUSIONS: Patch tests in the context of DRESS syndrome caused by antituberculosis drugs, despite their shortcomings, may potentially guide rapid retreatment of these patients.
- Biophysical characterization of mycobacterial model membranes and their interaction with rifabutin: Towards lipid-guided drug screening in tuberculosis. [Journal Article]
- BBBiochim Biophys Acta Biomembr 2019 Jun 01; 1861(6):1213-1227
- Lipid structure critically dictates the molecular interactions of drugs with membranes influencing passive diffusion, drug partitioning and accumulation, thereby underpinning a lipid-composition spec…
Lipid structure critically dictates the molecular interactions of drugs with membranes influencing passive diffusion, drug partitioning and accumulation, thereby underpinning a lipid-composition specific interplay. Spurring selective passive drug diffusion and uptake through membranes is an obvious solution to combat growing antibiotic resistance with minimized toxicities. However, the spectrum of complex mycobacterial lipids and lack thereof of suitable membrane platforms limits the understanding of mechanisms underlying drug-membrane interactions in tuberculosis. Herein, we developed membrane scaffolds specific to mycobacterial outer membrane and demonstrate them as improvised research platforms for investigating anti-tubercular drug interactions. Combined spectroscopy and microscopy results reveal an enhanced partitioning of model drug Rifabutin in trehalose dimycolate-containing mycobacterial membrane systems. These effects are apportioned to specific changes in membrane structure, order and fluidity leading to enhanced drug interaction. These findings on the membrane biophysical consequences of drug interactions will offer valuable insights for guiding the design of more effective antibiotic drugs coupled with tuned toxicity profiles.
- Reconciliation of Recent Helicobacter pylori Treatment Guidelines in a Time of Increasing Resistance to Antibiotics. [Review]
- GGastroenterology 2019 Apr 15
- Increasing resistance to antibiotics worldwide has adverse effects on the effectiveness of standard therapies to eradicate Helicobacter pylori infection. We reviewed guidelines developed by expert gr…
Increasing resistance to antibiotics worldwide has adverse effects on the effectiveness of standard therapies to eradicate Helicobacter pylori infection. We reviewed guidelines developed by expert groups in Europe, Canada, and the United States for the treatment of H pylori infection. We compared the recommendations of these guidelines, reconciled them, and addressed the increasing resistance of H pylori to antibiotic therapy regimens. The guidelines recommend bismuth for first-line treatment, replacing clarithromycin-based triple therapy. There is consensus for concomitant 4-drug therapy as an alternative, especially when bismuth is not available. When therapy is unsuccessful, it is likely due to resistance to clarithromycin, levofloxacin, and/or metronidazole; these drugs, if used previously, should be avoided in subsequent eradication attempts. Second-line therapies should be bismuth quadruple therapy or levofloxacin triple therapy, depending on suspected resistance, reserving rifabutin-based triple and high-dose dual amoxicillin proton pump inhibitor therapy for subsequent treatment attempts The increasing resistance of H pylori to antibiotic therapy necessitates local availability of susceptibility tests for individuals, and establishment of regional and national monitoring programs to develop evidence-based locally relevant eradication strategies. Further studies into the development of more easily accessible methods of resistance testing, such as biomarker analysis of stool samples, are required. Options under investigation include substituting vonoprazan for proton pump inhibitors, adding probiotics, and vaccine development. Narrow-spectrum antibiotics and new therapeutic targets could be identified based on genomic, proteomic, and metabolomic analyses of H pylori.
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- Inhalable chitosan microparticles for simultaneous delivery of isoniazid and rifabutin in lung tuberculosis treatment. [Journal Article]
- DDDrug Dev Ind Pharm 2019 Apr 16; :1-8
- The direct delivery of antibiotics to the lung has been considered an effective approach to treat pulmonary tuberculosis, which represents approximately 80% of total cases. In this sense, this work a…
The direct delivery of antibiotics to the lung has been considered an effective approach to treat pulmonary tuberculosis, which represents approximately 80% of total cases. In this sense, this work aimed at producing inhalable chitosan microparticles simultaneously associating isoniazid and rifabutin, for an application in pulmonary tuberculosis therapy. Spray-dried chitosan microparticles were obtained with adequate flow properties for deep lung delivery (aerodynamic diameter of 4 µm) and high drug association efficiencies (93% for isoniazid and 99% for rifabutin). The highest concentration of microparticles that was tested (1 mg/mL) decreased the viability of macrophage-differentiated THP-1 cells to around 60% after 24 h exposure, although no deleterious effect was observed in human alveolar epithelial (A549) cells. The release of LDH was, however, increased in both cells. Chitosan microparticles further evidenced capacity to activate macrophage-like cells, inducing cytokine secretion well above basal levels. Moreover, the propensity of macrophages to internalize microparticles was demonstrated, with uptake levels over 90%. Chitosan microparticles also inhibited bacterial growth by 96%, demonstrating that the microencapsulation preserved drug antibacterial activity in vitro. Overall, the obtained data suggest the potential of chitosan microparticles for inhalable lung tuberculosis therapy.