OBJECTIVE: The objective of this study was to identify whether the epithelial lining fluid components inhibit amikacin-mediated bacterial killing.
METHODS: Two amikacin-susceptible (minimum inhibitory concentrations of 2 and 8 mg/L) Pseudomonas aeruginosa isolates were exposed in vitro to amikacin concentrations up to 976 mg/L in the presence of an acidic pH, mucin and/or surfactant as a means of simulating the epithelial lining fluid, the site of bacterial infection in pneumonia. Pharmacodynamic modelling was used to describe associations between amikacin concentrations, bacterial killing and emergence of resistance.
RESULTS: In the presence of broth alone, there was rapid and extensive (> 6 - log10) bacterial killing, with emergence of resistance identified in amikacin concentrations < 976 mg/L. In contrast, the rate and extent of bacterial killing was reduced (≤ 5 - log10) when exposed to an acidic pH and mucin. Surfactant did not appreciably impact the bacterial killing or resistance emergence when compared with broth alone for either isolate. The combination of mucin and an acidic pH further reduced the rate of bacterial killing, with the maximal bacterial killing occurring 24 h following initial exposure compared with approximately 4-8 h for either mucin or an acidic pH alone.
CONCLUSIONS: Our findings indicate that simulating the epithelial lining fluid antagonises amikacin-mediated killing of P. aeruginosa, even at the high concentrations achieved following nebulised administration.
METHODS: Currently available indicators from both household and facility surveys were collated through publicly available global databases and respective survey instruments. We then developed a suite of potential indicators and associated data points for the 45 WHO Essential Interventions spanning preconception to newborn care. Four types of performance indicators were identified (where applicable): process (i.e. coverage) and outcome (i.e. impact) indicators for both screening and treatment/prevention. Indicators were evaluated by an international expert panel against the eRegistries indicator evaluation criteria and further refined based on feedback by the eRegistries technical team.
RESULTS: Of the 45 WHO Essential Interventions, only 16 were addressed in any of the household survey data available. A set of 216 potential indicators was developed. These indicators were generally evaluated favourably by the panel, but difficulties in data ascertainment, including for outcome measures of cause-specific morbidity and mortality, were frequently reported as barriers to the feasibility of indicators. Indicators were refined based on feedback, culminating in the final list of 193 total unique indicators: 93 for preconception and antenatal care; 53 for childbirth and postpartum care; and 47 for newborn and small and ill baby care.
CONCLUSIONS: Large gaps exist in the availability of information currently collected to support the implementation of the WHO Essential Interventions. The development of this suite of indicators can be used to support the implementation of eRegistries and other data platforms, to ensure that data are utilised to support evidence-based practice, facilitate measurement and accountability, and improve maternal and child health outcomes.