An Observational Laboratory-Based Assessment of SARS-CoV-2 Molecular Diagnostics in Benin, Western Africa.

Information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread in Africa is limited by insufficient diagnostic capacity. Here, we assessed the coronavirus disease (COVID-19)-related diagnostic workload during the onset of the pandemic in the central laboratory of Benin, Western Africa; characterized 12 SARS-CoV-2 genomes from returning travelers; and validated the Da An RT-PCR-based diagnostic kit that is widely used across Africa. We found a 15-fold increase in the monthly laboratory workload due to COVID-19, dealt with at the cost of routine activities. Genomic surveillance showed near-simultaneous introduction of distinct SARS-CoV-2 lineages termed A.4 and B.1, including the D614G spike protein variant potentially associated with higher transmissibility from travelers from six different European and African countries during March-April 2020. We decoded the target regions within the ORF1ab and N genes of the Da An dual-target kit by MinION-based amplicon sequencing. Despite relatively high similarity between SARS-CoV-2 and endemic human coronaviruses (HCoVs) within the ORF1ab target domain, no cross-detection of high-titered cell culture supernatants of HCoVs was observed, suggesting high analytical specificity. The Da An kit was highly sensitive, detecting 3.2 to 9.0 copies of target-specific in vitro transcripts/reaction. Although discrepant test results were observed in low-titered clinical samples, clinical sensitivity of the Da An kit was at least comparable to that of commercial kits from affluent settings. In sum, virologic diagnostics are achievable in a resource-limited setting, but unprecedented pressure resulting from COVID-19-related diagnostics requires rapid and sustainable support of national and supranational stakeholders addressing limited laboratory capacity.IMPORTANCE Months after the start of the COVID-19 pandemic, case numbers from Africa are surprisingly low, potentially because the number of SARS-CoV-2 tests performed in Africa is lower than in other regions. Here, we show an overload of COVID-19-related diagnostics in the central laboratory of Benin, Western Africa, with a stagnating average number of positive samples irrespective of daily sample counts. SARS-CoV-2 genomic surveillance confirmed a high genomic diversity in Benin introduced by travelers returning from Europe and other African countries, including early circulation of the D614G spike mutation associated with potentially higher transmissibility. We validated a widely used RT-PCR kit donated by the Chinese Jack Ma Foundation and confirmed high analytical specificity and clinical sensitivity equivalent to tests used in affluent settings. Our assessment shows that although achievable in an African setting, the burden from COVID-19-related diagnostics on national reference laboratories is very high.

Long-term impact of competitive biddings and an antimicrobial stewardship program in a general hospital in Chile / Impacto de un programa de control de antimicrobianos (PCA) y licitaciones públicas sobre el consumo de estos medicamentos

ABSTRACT Background: The long-term effect of an antimicrobial stewardship program (ASP) and its integrated impact with competitive biddings have been seldom reported. Aim: To evaluate the long-term effect of an ASP on antimicrobial consumption, expenditure, antimicrobial resistance and hospital mortality. To estimate the contribution of competitive biddings on cost-savings. Material and Methods: A comparison of periods prior (2005-2008) and posterior to ASP initiation (2009 and 2015) was done. An estimation of cost savings attributable to ASP and to competitive biddings was also performed. Results: Basal median antimicrobial consumption decreased from 221.3 to 170 daily defined doses/100 beds after the start of the ASP. At the last year, global antimicrobial consumption declined by 28%. Median antimicrobial expenditure per bed (initially US$ 13) declined to US$ 10 at the first year (-28%) and to US$ 6 the last year (-57%). As the reduction in consumption was lower than the reduction in expenditure during the last year, we assumed that only 48.4% of savings were attributable to the ASP. According to antimicrobial charges per bed from prior and after ASP implementation, we estimated global savings of US$ 393072 and US$ 190000 directly attributable to the ASP, difference explained by parallel competitive biddings. Drug resistance among nosocomial bacterial isolates did not show significant changes. Global and infectious disease-associated mortality per 1000 discharges significantly decreased during the study period (p < 0.05). Conclusions: The ASP had a favorable impact on antimicrobial consumption, savings and mortality rates but did not have effect on antimicrobial resistance in selected bacterial strains.

Antecedentes: Existe poca información sobre el impacto a largo plazo de un programa de control de antimicrobianos (PCA) y su efecto combinado con licitaciones públicas de fármacos. Objetivo: Evaluar el impacto de un PCA sobre el consumo, gasto, mortalidad y estimar la contribución de las licitaciones. Material y Métodos: Comparación antes (2005-2008) - después (2009-2015) del PCA y estimación porcentual del ahorro atribuible al PCA y licitaciones. Resultados: El consumo bajó de 221,3 a 170 dosis diarias definidas por 100 días camas (medianas) al primer año. En el último año el consumo declinó un 27,6%. La mediana del gasto por cama ocupada se redujo de 13 a 10 US$ el primer año y a 6 US$ el último año (-57%). Debido a que el gasto bajó más que el consumo, estimamos que solo el 48,4% del ahorro fue debido al PCA (cuociente de ambas reducciones: −27,6%/-57%). De acuerdo con el gasto en antimicrobianos por cama entre ambos períodos, se calculó un ahorro global de 393.000 US$ y de 190.000 US$ directamente atribuible al PCA, siendo la diferencia explicada por licitaciones. Los porcentajes de resistencia en cepas de infecciones nosocomiales no mostraron incrementos o reducciones significativas en el tiempo y la mortalidad por egresos asociada a enfermedades infecciosas (Códigos CIE 10) se redujo significativamente (p < 0,05). Conclusiones: El PCA se asoció a largo plazo a un impacto favorable sobre el consumo de antimicrobianos, gasto por antimicrobianos y egresos por enfermedades infecciosas sin un impacto en la resistencia antimicrobiana. Las licitaciones tuvieron un efecto aditivo en el ahorro.

Long-term impact of competitive biddings and an antimicrobial stewardship program in a general hospital in Chile.

BACKGROUND: The long-term effect of an antimicrobial stewardship program (ASP) and its integrated impact with competitive biddings have been seldom reported. AIM: To evaluate the long-term effect of an ASP on antimicrobial consumption, expenditure, antimicrobial resistance and hospital mortality. To estimate the contribution of competitive biddings on cost-savings. MATERIAL AND METHODS: A comparison of periods prior (2005-2008) and posterior to ASP initiation (2009 and 2015) was done. An estimation of cost savings attributable to ASP and to competitive biddings was also performed. RESULTS: Basal median antimicrobial consumption decreased from 221.3 to 170 daily defined doses/100 beds after the start of the ASP. At the last year, global antimicrobial consumption declined by 28%. Median antimicrobial expenditure per bed (initially US$ 13) declined to US$ 10 at the first year (-28%) and to US$ 6 the last year (-57%). As the reduction in consumption was lower than the reduction in expenditure during the last year, we assumed that only 48.4% of savings were attributable to the ASP. According to antimicrobial charges per bed from prior and after ASP implementation, we estimated global savings of US$ 393072 and US$ 190000 directly attributable to the ASP, difference explained by parallel competitive biddings. Drug resistance among nosocomial bacterial isolates did not show significant changes. Global and infectious disease-associated mortality per 1000 discharges significantly decreased during the study period (p < 0.05). CONCLUSIONS: The ASP had a favorable impact on antimicrobial consumption, savings and mortality rates but did not have effect on antimicrobial resistance in selected bacterial strains.

Cotrimoxazol en infecciones óseas: toxicidad e impacto clínico y económico / Cotrimoxazole in bone-related infections: toxicity and clinical and economic impact

Background: Cotrimoxazole is a therapeutic option for bone-related infections but is associated to hyperkalemia and renal failure. Tolerance to this drug may reduce length of stay (LOS) and hospital charges. Aims: To evaluate renal, potassium toxicity, clinical outcome, and use of hospital resources in patients treated with cotrimoxazole for bone-related infections. Methods: Retrospective analysis of adult patients with bone-related infections confirmed by culture and treated with this drug. Serum potassium and creatinine levels were analyzed during follow-up and risk factors for hyperkalemia were searched. Length of stay (LOS) and hospital charges were compared. Clinical outcome was evaluated as a secondary endpoint. Results: From 2011 to 2014, 23 patients were identified (mean age 64.7 years). Diabetes mellitus, peripheral vascular disease, and previous amputations prevalence were high (82.6%, 47.8%, and 43.5%, respectively). Median serum potassium concentration increased significantly at first control (4.35 mEq/L to 4.9 mEq/L; p < 0.001), and also creatinine serum concentration (0.9 to 1.1 mg/dL; p < 0.05). Seven patients developed hyperkalemia. Cotrimoxazole was discontinued in 10 patients (43.5%), and in 6, discharge was postponed. Drugs active against the renin-angiotensin system (DAARAS) were associated with kyperkalemia (OR 10.8 IC95 1.37-85; p < 0.05). LOS was higher among patients with cotrimoxazole toxicity (median LOS 56 versus 30 days, p < 0.05). Patients with no cotrimoxazole interruption had less drug-related hospital charges (median values of 563 versus 2820 USD, respectively; p < 0.01). Conclusions: Cotrimoxazole use must be monitored in order to detect hyperkalemia or renal toxicity and suspend its prescription. Patients that use DAARAS have a higher risk of kyperkalemia. LOS and drug-related hospital charges are reduced when patients can tolerate cotrimoxazole.

Antecedentes: Cotrimoxazol es una alternativa en infecciones óseas pero se ha asociado al desarrollo de falla renal e hiperkalemia. Objetivo: Evaluar toxicidad renal, hiperkalemia, estadía y gastos hospitalarios y evolución clínica en un grupo de pacientes con infecciones óseas tratados con este compuesto. Pacientes y Métodos: Estudio retrospectivo-descriptivo de pacientes adultos con infecciones óseas confirmadas con cultivos y tratados con este compuesto. Seguimiento de creatinina y kalemia y búsqueda de factores de riesgo para hiperkalemia, comparación de gastos y estadía hospitalaria y análisis de eficacia clínica. Resultados: Desde el año 2011 al 2014 se identificaron 23 pacientes (promedio de edad 64,7 años). La prevalencia de diabetes mellitus tipo 2 (82,6%), enfermedad vascular periférica (47,8%) y amputaciones previas (43,5%) fue elevada. La mediana de la kalemia basal aumentó significativamente al primer control (4,35 a 4,9 mEq/L) al igual que la creatinina plasmática (0,9 a 1,1 mg/dL). Siete pacientes desarrollaron hiperkalemia (30,4%). Se suspendió cotrimoxazol en 10 casos (43,5%) y en 6 casos se postergó el alta. El uso de fármacos activos contra el sistema renina-angiotensina (FASRA) se asoció a hiperkalemia (OR 10,8 IC95 1,37-85; p < 0,05). La estadía hospitalaria fue mayor en el grupo con toxicidad a cotrimoxazol (mediana de 56 versus 30 días; p < 0,05) y los pacientes sin suspensión de terapia tuvieron menos gastos por fármacos (medianas de 563 vs 2.820 USD, p < 0,01). Conclusiones: El uso de cotrimoxazol debe ser monitorizado para detectar hiperkalemia o toxicidad renal y suspender su prescripción. Los pacientes que usan FASRA tienen mayor riesgo de hiperkalemia. La estadía y gastos hospitalarios por fármacos son menores en pacientes que toleran el cotrimoxazol.

[Cotrimoxazole in bone-related infections: toxicity and clinical and economic impact]. / Cotrimoxazol en infecciones óseas: toxicidad e impacto clínico y económico.

BACKGROUND: Cotrimoxazole is a therapeutic option for bone-related infections but is associated to hyperkalemia and renal failure. Tolerance to this drug may reduce length of stay (LOS) and hospital charges. AIMS: To evaluate renal, potassium toxicity, clinical outcome, and use of hospital resources in patients treated with cotrimoxazole for bone-related infections. METHODS: Retrospective analysis of adult patients with bone-related infections confirmed by culture and treated with this drug. Serum potassium and creatinine levels were analyzed during follow-up and risk factors for hyperkalemia were searched. Length of stay (LOS) and hospital charges were compared. Clinical outcome was evaluated as a secondary endpoint. RESULTS: From 2011 to 2014, 23 patients were identified (mean age 64.7 years). Diabetes mellitus, peripheral vascular disease, and previous amputations prevalence were high (82.6%, 47.8%, and 43.5%, respectively). Median serum potassium concentration increased significantly at first control (4.35 mEq/L to 4.9 mEq/L; p < 0.001), and also creatinine serum concentration (0.9 to 1.1 mg/dL; p < 0.05). Seven patients developed hyperkalemia. Cotrimoxazole was discontinued in 10 patients (43.5%), and in 6, discharge was postponed. Drugs active against the renin-angiotensin system (DAARAS) were associated with kyperkalemia (OR 10.8 IC95 1.37-85; p < 0.05). LOS was higher among patients with cotrimoxazole toxicity (median LOS 56 versus 30 days, p < 0.05). Patients with no cotrimoxazole interruption had less drug-related hospital charges (median values of 563 versus 2820 USD, respectively; p < 0.01). CONCLUSIONS: Cotrimoxazole use must be monitored in order to detect hyperkalemia or renal toxicity and suspend its prescription. Patients that use DAARAS have a higher risk of kyperkalemia. LOS and drug-related hospital charges are reduced when patients can tolerate cotrimoxazole.