Adequate plasma drug concentrations suggest that amoxicillin can be administered by continuous infusion using elastomeric pumps.

Elastomeric pumps can be useful for the administration of antibiotics in the outpatient setting. To determine amoxicillin degradation in elastomeric pumps, as well as the effectiveness of amoxicillin treatment administered by elastomeric pumps. Antibiotic degradation was measured in elastomeric pumps filled with 6 g of amoxicillin in 240 mL of NaCl 0.9% by drawing samples at 12 h intervals when stored in the fridge for 48 h and when worn around the waist for 24 h. Subsequently nine patients were treated with continuous infusions of 8 or 12 g of amoxicillin per day. Plasma amoxicillin concentrations were measured on each visit to the outpatient parenteral antibiotic therapy unit. Clinical outcome was verified 3 months after the end of treatment. Amoxicillin degradation in elastomeric pumps reached 10% after 48 h in the fridge and an additional 30% when worn around the waist for 24 h. Mean plasma drug concentrations achieved with 12 g of amoxicillin per day were 18.5 mg/L (95% CI 13.5-23.5), which is largely above the MIC of amoxicillin-susceptible bacteria. Nine patients treated for various complicated infections were cured and had no unexpected adverse effects. Adequate plasma drug concentrations and favourable clinical outcomes suggest that amoxicillin can be administered by continuous infusion using elastomeric pumps. This treatment modality does not fulfil formal requirements regarding pharmaceutical stability, but the resulting safety impact in patients is probably limited. Therapeutic drug monitoring and a close clinical follow-up are recommended if this route of administration is chosen

Nearly Complete Genome Sequence of a Novel Phlebovirus-Like Virus Detected in a Human Plasma Sample by High-Throughput Sequencing.

Here, we report a novel phlebovirus-like virus sequence detected in a plasma sample from a febrile adult patient collected in the United Republic of Tanzania in 2014. A nearly complete RNA sequence was generated by high-throughput sequencing on a HiSeq 2500 instrument and further confirmed after repeating the analysis, starting from the initial sample

COVID-19 risk stratification algorithms based on sTREM-1 and IL-6 in emergency department.

The coronavirus disease 2019 (COVID-19) pandemic has led to surges of patients presenting to emergency departments (EDs) and potentially overwhelming health systems. We sought to assess the predictive accuracy of host biomarkers at clinical presentation to the ED for adverse outcome. Prospective observational study of PCR-confirmed COVID-19 patients in the ED of a Swiss hospital. Concentrations of inflammatory and endothelial dysfunction biomarkers were determined at clinical presentation. We evaluated the accuracy of clinical signs and these biomarkers in predicting 30-day intubation/mortality, and oxygen requirement by calculating the area under the receiver-operating characteristic curve and by classification and regression tree analysis. Of 76 included patients with COVID-19, 24 were outpatients or hospitalized without oxygen requirement, 35 hospitalized with oxygen requirement, and 17 intubated/died. We found that soluble triggering receptor expressed on myeloid cells had the best prognostic accuracy for 30-day intubation/mortality (area under the receiver-operating characteristic curve, 0.86; 95% CI, 0.77-0.95) and IL-6 measured at presentation to the ED had the best accuracy for 30-day oxygen requirement (area under the receiver-operating characteristic curve, 0.84; 95% CI, 0.74-0.94). An algorithm based on respiratory rate and sTREM-1 predicted 30-day intubation/mortality with 94% sensitivity and 0.1 negative likelihood ratio. An IL-6-based algorithm had 98% sensitivity and 0.04 negative likelihood ratio for 30-day oxygen requirement. sTREM-1 and IL-6 concentrations in COVID-19 in the ED have good predictive accuracy for intubation/mortality and oxygen requirement. sTREM-1- and IL-6-based algorithms are highly sensitive to identify patients with adverse outcome and could serve as early triage tools

Retrospective study on the usefulness of pulse oximetry for the identification of young children with severe illnesses and severe pneumonia in a rural outpatient clinic of Papua New Guinea.

This secondary analysis of data of a randomized controlled trial (RCT) retrospectively investigated the performance of pulse oximetry in identifying children with severe illnesses, with and without respiratory signs/symptoms, in a cohort of children followed for morbid episodes in an intervention trial assessing the efficacy of Intermittent Preventive Treatment for malaria in infants (IPTi) in Papua New Guinea (PNG) from June 2006 to May 2010. The IPTi study was conducted in a paediatric population visiting two health centres on the north coast of PNG in the Mugil area of the Sumkar District. A total of 669 children visited the clinic and a total of 1921 illness episodes were recorded. Inclusion criteria were: age between 3 and 27 months, full clinical record (signs/symptoms) and pulse oximetry used systematically to assess sick children at all visits. Children were excluded if they visited the clinic in the previous 14 days. The outcome measures were severe illness, severe pneumonia, pneumonia, defined by the Integrated Management of Childhood Illness (IMCI) definitions, and hospitalization. Out of 1921 illness episodes, 1663 fulfilled the inclusion criteria. A total of 139 severe illnesses were identified, of which 93 were severe pneumonia. The ROC curves of pulse oximetry (continuous variable) showed an AUC of 0.63, 0.68 and 0.65 for prediction of severe illness, severe pneumonia and hospitalization, respectively. Pulse oximetry allowed better discrimination between severe and non-severe illness, severe and non-severe pneumonia, admitted and non-admitted patients, in children ≤12-months of age relative to older patients. For the threshold of peripheral arterial oxygen saturation ≤ 94% measured by pulse oximetry (SpO2), unadjusted odds ratios for severe illness, severe pneumonia and hospitalization were 6.1 (95% Confidence Interval (CI) 3.9-9.8), 8.5 (4.9-14.6) and 5.9 (3.4-10.3), respectively. Pulse oximetry was helpful in identifying children with severe illness in outpatient facilities in PNG. A SpO2 of 94% seems the most discriminative threshold. Considering its affordability and ease of use, pulse oximetry could be a valuable additional tool assisting the decision to admit for treatment

Pulse Oximetry as an Aid to Rule Out Pneumonia among Patients with a Lower Respiratory Tract Infection in Primary Care.

Guidelines recommend chest X-rays (CXRs) to diagnose pneumonia and guide antibiotic treatment. This study aimed to identify clinical predictors of pneumonia that are visible on a chest X-ray (CXR+) which could support ruling out pneumonia and avoiding unnecessary CXRs, including oxygen saturation. A secondary analysis was performed in a clinical trial that included patients with suspected pneumonia in Swiss primary care. CXRs were reviewed by two radiologists. We evaluated the association between clinical signs (heart rate > 100/min, respiratory rate ≥ 24/min, temperature ≥ 37.8 °C, abnormal auscultation, and oxygen saturation < 95%) and CXR+ using multivariate analysis. We also calculated the diagnostic performance of the associated clinical signs combined in a clinical decision rule (CDR), as well as a CDR derived from a large meta-analysis (at least one of the following: heart rate > 100/min, respiratory rate ≥ 24/min, temperature ≥ 37.8 °C, or abnormal auscultation). Out of 469 patients from the initial trial, 107 had a CXR and were included in this study. Of these, 26 (24%) had a CXR+. We found that temperature and oxygen saturation were associated with CXR+. A CDR based on the presence of either temperature ≥ 37.8 °C and/or an oxygen saturation level < 95% had a sensitivity of 69% and a negative likelihood ratio (LR-) of 0.45. The CDR from the meta-analysis had a sensitivity of 92% and an LR- of 0.37. The addition of saturation < 95% to this CDR increased the sensitivity (96%) and decreased the LR- (0.21). In conclusion, this study suggests that pulse oximetry could be added to a simple CDR to decrease the probability of pneumonia to an acceptable level and avoid unnecessary CXRs

Patient satisfaction in an outpatient parenteral antimicrobial therapy (OPAT) unit practising predominantly self-administration of antibiotics with elastomeric pumps.

Self-administration of antibiotics using elastomeric pumps has become the most frequently used treatment modality at the outpatient parenteral antimicrobial therapy (OPAT) unit of the University Hospital of Lausanne. However, it remains unknown how comfortable patients feel using this mode of treatment. A questionnaire was offered to all patients treated at the OPAT unit between June 2014 and December 2015. The questionnaire was distributed to 188 patients and 112 questionnaires were returned. Seventy-one patients were treated by self-administration, 21 attended the OPAT unit on a daily basis, and 20 received their antibiotics from home-care nurses. Overall, 83-97% of the patients gave the highest possible scores to the four items evaluating their global satisfaction. Subjects treated by self-administration gave a significantly better rating to 6 of the 17 semi-quantitative questions than the patients treated at the OPAT unit or by home-care nurses. There was no item which was more poorly rated by patients treated by self-administered OPAT than by the other treatment groups. In conclusion satisfaction was high in all patients treated by OPAT. The particularly high satisfaction of patients treated by self-administration of antibiotics with elastomeric pumps suggests that a significant number of patients are happy to take over some responsibility for their treatment. Patients' capacity to appropriate their care themselves should not be underestimated by health care professionals

Efficacy and safety of continuous infusions with elastomeric pumps for outpatient parenteral antimicrobial therapy (OPAT): an observational study.

This study aimed to evaluate the efficacy and safety of continuous antimicrobial infusion using elastomeric pumps in an outpatient setting, while simultaneously documenting circulating antibiotic concentration exposure achieved with this mode of administration. Clinical outcomes, adverse events and antibiotic plasma concentrations were recorded for all patients treated by continuous infusion with elastomeric pumps at the outpatient parenteral antimicrobial therapy (OPAT) unit of the University Hospital of Lausanne between December 2013 and January 2017. The study was registered under ClinicalTrials.gov identifier NCT03221140. One hundred and fifty outpatients were treated by continuous intravenous infusions using flucloxacillin (70 patients), cefepime (36), vancomycin (32) and piperacillin/tazobactam (12). The calculated free fractions of each antibiotic were above the epidemiological cut-off values for resistance (ECOFF) of the treated microorganisms in 92% of measurements. Cure was achieved in 143 patients (95%) 3 months after the end of treatment. Four patients needed unexpected readmission and three had a relapse. In none of the patients with unsuccessful treatment was the ratio of free antibiotic plasma concentration/ECOFF <1. Sixteen patients (11%) had an adverse event, none of them being of severity grade 4 or 5. Continuous infusions of flucloxacillin, cefepime, vancomycin and piperacillin/tazobactam using elastomeric pumps seem to be an effective and safe approach to treat outpatients. The number of treatment successes was very high and adverse events occurred at a similar rate as reported by other OPAT centres. The measured antibiotic plasma concentrations confirmed adequate drug concentration exposure for the vast majority of patients

Brief Report: Switching From TDF to TAF in HIV/HBV-Coinfected Individuals With Renal Dysfunction-A Prospective Cohort Study.

Whereas tenofovir disoproxil fumarate (TDF) can lead to renal adverse events, tenofovir alafenamide (TAF) has a more favorable renal safety profile. However, the impact of replacing TDF with TAF on renal function and liver parameters among HIV/hepatitis B virus (HBV)-coinfected individuals with renal dysfunction remains unclear. We included all participants from the Swiss HIV Cohort Study with an HIV/HBV coinfection who switched from TDF to TAF and had an estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m and a suppressed HIV viral load (<200 cp/mL). We assessed changes in eGFR, urine protein-to-creatinine ratio, and alanine aminotransferase (ALT) after 1 year using mixed-effect models with interrupted time series. Among 106 participants (15.1% women, median age 53 years), eGFR was 60-89 mL/min/1.73 m in 84 (79.2%) and <60 mL/min/1.73 m in 22 (20.8%) individuals at the time of switch. One year after the switch from TDF to TAF, individuals with an eGFR between 60 and 89 mL/min/1.73 m experienced increases in eGFR of 3.2 mL/min/1.73 m (95% confidence interval [CI] 1.2 to 5.2), whereas those with an eGFR <60 mL/min/1.73 m experienced improvements of 6.2 mL/min/1.73 m (95% CI 2.4 to 10.0). Urine protein-to-creatinine ratio decreased overall (-6.3 mg/mmol, 95% CI -10.0 to -2.7), and ALT levels declined in patients with elevated baseline levels (-11.8 IU/L, 95% CI -17.3 to -6.4) 1 year after replacing TDF with TAF. Switching from TDF to TAF among HIV/HBV-coinfected individuals with renal impairment led to improvements in eGFR, a decline in proteinuria, and to ALT normalization in those with elevated ALT levels

Diagnostic Performance of Conventional and Ultrasensitive Rapid Diagnostic Tests for Malaria in Febrile Outpatients in Tanzania.

A novel ultrasensitive malaria rapid diagnostic test (us-RDT) has been developed for improved active Plasmodium falciparum infection detection. The usefulness of this us-RDT in clinical diagnosis and fever management has not been evaluated. Diagnostic performance of us-RDT was compared retrospectively to that of conventional RDT (co-RDT) in 3000 children and 515 adults presenting with fever to Tanzanian outpatient clinics. The parasite density was measured by an ultrasensitive qPCR (us-qPCR), and the HRP2 concentration was measured by an enzyme-linked immunosorbent assay. us-RDT identified few additional P. falciparum-positive patients as compared to co-RDT (276 vs 265 parasite-positive patients detected), with only a marginally greater sensitivity (75% vs 73%), using us-qPCR as the gold standard (357 parasite-positive patients detected). The specificity of both RDTs was >99%. Five of 11 additional patients testing positive by us-RDT had negative results by us-qPCR. The HRP2 concentration was above the limit of detection for co-RDT (>3653 pg of HRP2 per mL of blood) in almost all infections (99% [236 of 239]) with a parasite density >100 parasites per µL of blood. At parasite densities <100 parasites/µL, the HRP2 concentration was above the limits of detection of us-RDT (>793 pg/mL) and co-RDT in 29 (25%) and 24 (20%) of 118 patients, respectively. There is neither an advantage nor a risk of using us-RDT, rather than co-RDT, for clinical malaria diagnosis. In febrile patients, only a small proportion of infections are characterized by a parasite density or an HRP2 concentration in the range where use of us-RDT would confer a meaningful advantage over co-RDT