Comparison of Antimicrobial Stewardship and Infection Prevention and Control Activities and Resources Between Low-/Middle- and High-income Countries.

BACKGROUND: The growth of antimicrobial resistance worldwide has led to increased focus on antimicrobial stewardship (AMS) and infection prevention and control (IPC) measures, although primarily in high-income countries (HIC). We aimed to compare pediatric AMS and IPC resources/activities between low- and middle-income countries (LMIC) and HIC and to determine the barriers and priorities for AMS and IPC in LMIC as assessed by clinicians in those settings. METHODS: An online questionnaire was distributed to clinicians working in HIC and LMIC healthcare facilities in 2020. RESULTS: Participants were from 135 healthcare settings in 39 LMIC and 27 HIC. Formal AMS and IPC programs were less frequent in LMIC than HIC settings (AMS 42% versus 76% and IPC 58% versus 89%). Only 47% of LMIC facilities conducted audits of antibiotic use for pediatric patients, with less reliable availability of World Health Organization Access list antibiotics (29% of LMIC facilities). Hand hygiene promotion was the most common IPC intervention in both LMIC and HIC settings (82% versus 91%), although LMIC hospitals had more limited access to reliable water supply for handwashing and antiseptic hand rub. The greatest perceived barrier to pediatric AMS and IPC in both LMIC and HIC was lack of education: only 17% of LMIC settings had regular/required education on antimicrobial prescribing and only 25% on IPC. CONCLUSIONS: Marked differences exist in availability of AMS and IPC resources in LMIC as compared with HIC. A collaborative international approach is urgently needed to combat antimicrobial resistance, using targeted strategies that address the imbalance in global AMS and IPC resource availability and activities.

HIV-1 Persistence in Children during Suppressive ART.

There is a growing number of perinatally HIV-1-infected children worldwide who must maintain life-long ART. In early life, HIV-1 infection is established in an immunologically inexperienced environment in which maternal ART and immune dynamics during pregnancy play a role in reservoir establishment. Children that initiated early antiretroviral therapy (ART) and maintained long-term suppression of viremia have smaller and less diverse HIV reservoirs than adults, although their proviral landscape during ART is reported to be similar to that of adults. The ability of these early infected cells to persist long-term through clonal expansion poses a major barrier to finding a cure. Furthermore, the effects of life-long HIV persistence and ART are yet to be understood, but growing evidence suggests that these individuals are at an increased risk for developing non-AIDS-related comorbidities, which underscores the need for an HIV cure.

Accelerating Clinical Evaluation of Repurposed Combination Therapies for COVID-19.

As the global COVID-19 pandemic continues, unabated and clinical trials demonstrate limited effective pharmaceutical interventions, there is a pressing need to accelerate treatment evaluations. Among options for accelerated development is the evaluation of drug combinations in the absence of prior monotherapy data. This approach is appealing for a number of reasons. First, combining two or more drugs with related or complementary therapeutic effects permits a multipronged approach addressing the variable pathways of the disease. Second, if an individual component of a combination offers a therapeutic effect, then in the absence of antagonism, a trial of combination therapy should still detect individual efficacy. Third, this strategy is time saving. Rather than taking a stepwise approach to evaluating monotherapies, this strategy begins with testing all relevant therapeutic options. Finally, given the severity of the current pandemic and the absence of treatment options, the likelihood of detecting a treatment effect with combination therapy maintains scientific enthusiasm for evaluating repurposed treatments. Antiviral combination selection can be facilitated by insights regarding SARS-CoV-2 pathophysiology and cell cycle dynamics, supported by infectious disease and clinical pharmacology expert advice. We describe a clinical evaluation strategy using adaptive combination platform trials to rapidly test combination therapies to treat COVID-19.