3 research outputs found
Therapeutic drug monitoring in patients with tuberculosis and concurrent medical problems
Introduction Therapeutic drug monitoring (TDM) has been recommended for treatment optimization in tuberculosis (TB) but is only is used in certain countries e.g. USA, Germany, the Netherlands, Sweden and Tanzania. Recently, new drugs have emerged and PK studies in TB are continuing, which contributes further evidence for TDM in TB. The aim of this review is to provide an update on drugs used in TB, treatment strategies for these drugs, and TDM to support broader implementation. Areas covered This review describes the different drug classes used for TB, multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB), along with their pharmacokinetics, dosing strategies, TDM and sampling strategies. Moreover, the review discusses TDM for patient TB and renal or liver impairment, patients co-infected with HIV or hepatitis, and special patient populations - children and pregnant women. Expert opinion TB treatment has a long history of using 'one size fits all.' This has contributed to treatment failures, treatment relapses, and the selection of drug-resistant isolates. While challenging in resource-limited circumstances, TDM offers the clinician the opportunity to individualize and optimize treatment early in treatment. This approach may help to refine treatment and thereby reduce adverse effects and poor treatment outcomes. Funding, training, and randomized controlled trials are needed to advance the use of TDM for patients with TB
Structure–Activity Relationships of a Diverse Class of Halogenated Phenazines That Targets Persistent, Antibiotic-Tolerant Bacterial Biofilms and <i>Mycobacterium tuberculosis</i>
Persistent bacteria,
including persister cells within surface-attached
biofilms and slow-growing pathogens lead to chronic infections that
are tolerant to antibiotics. Here, we describe the structure–activity
relationships of a series of halogenated phenazines (HP) inspired
by 2-bromo-1-hydroxyphenazine <b>1</b>. Using multiple synthetic
pathways, we probed diverse substitutions of the HP scaffold in the
2-, 4-, 7-, and 8-positions, providing critical information regarding
their antibacterial and bacterial eradication profiles. Halogenated
phenazine <b>14</b> proved to be the most potent biofilm-eradicating
agent (≥99.9% persister cell killing) against MRSA (MBEC <
10 μM), MRSE (MBEC = 2.35 μM), and VRE (MBEC = 0.20 μM)
biofilms while <b>11</b> and <b>12</b> demonstrated excellent
antibacterial activity against <i>M. tuberculosis</i> (MIC
= 3.13 μM). Unlike antimicrobial peptide mimics that eradicate
biofilms through the general lysing of membranes, HPs do not lyse
red blood cells. HPs are promising agents that effectively target
persistent bacteria while demonstrating negligible toxicity against
mammalian cells