A new series of dual low nanomolar benzothiazole inhibitors
of
bacterial DNA gyrase and topoisomerase IV were developed. The resulting
compounds show excellent broad-spectrum antibacterial activities against
Gram-positive
Enterococcus faecalis
,
Enterococcus faecium
and multidrug
resistant (MDR)
Staphylococcus aureus
strains [best compound minimal inhibitory concentrations (MICs):
range, <0.03125–0.25 μg/mL] and against the Gram-negatives
Acinetobacter baumannii
and
Klebsiella
pneumoniae
(best compound MICs: range, 1–4
μg/mL). Lead compound
7a
was identified with favorable
solubility and plasma protein binding, good metabolic stability, selectivity
for bacterial topoisomerases, and no toxicity issues. The crystal
structure of
7a
in complex with
Pseudomonas
aeruginosa
GyrB24 revealed its binding mode at the
ATP-binding site. Expanded profiling of
7a
and
7h
showed potent antibacterial activity against over 100 MDR
and non-MDR strains of
A. baumannii
and several other Gram-positive and Gram-negative strains. Ultimately,
in vivo efficacy of
7a
in a mouse model of vancomycin-intermediate
S. aureus
thigh infection was also demonstrated.
The aim of this study is to investigate how the poor, relative to the wealthier, benefitted from recent improvements in health insurance coverage, maternity care utilisation (modern contraceptive use, antenatal care visits, facility delivery, and skilled birth attendants), and under-five mortality in Kenya. The analysis relies on the latest two waves of the Kenya Demographic and Health Survey and a theoretical framework with three different inclusiveness (pro-poorness) concepts. Our results are quite robust to pro-poorness concepts and poverty definitions. The main result is that the poor experienced larger improvements in all investigated health aspects compared to the rich (irrespective of the poverty concept) when changes are measured in relative terms. When we investigate changes in absolute terms, we find a similar pattern, except in the case of health insurance coverage and the presence of a skilled birth attendant during delivery. Our analysis is expected to inform policymaking aiming to achieve universal health coverage.
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