Notes

Alzheimer's Diagnostics Must Be Internationally Obtainable.
is a highly virulent and contagious Gram-negative intracellular bacterium that causes the disease tularaemia in mammals and is classified as a Category A priority pathogen.

We utilized a systematic analysis of antibacterial potency, extent of dissemination by analysis of bacterial burden in a secondary vital organ, and survival rates to assess the efficacy of a novel rifampicin derivative, TPR1. The efficacy of TPR1 was evaluated alone and in combination with the standard of care drug, doxycycline, against type A
Schu S4 using a lethal pulmonary model of infection in mice.

TPR1 has an MIC value range of 0.125-4 mg/L against reference laboratory strain Schu S4 and a panel of clinical strains. TPR1 alone reduced the bacterial burden in the lungs and spleen at 40 mg/kg and 80 mg/kg, and no antagonism was observed when co-administered with doxycycline. Dosing at 40 mg/kg doxycycline reduced the bacterial burden by 1 log
 cfu in the lungs and 4 log
 cfu in the spleen in comparison to untreated controls. Co-administration of TPR1 and doxycycline demonstrated efficacy upon treatment withdrawal after 4 days of treatment, and 100% survival.

Significantly, TPR1 demonstrated efficacy when delivered alone and in combination with doxycycline, which provides compelling evidence of a superior treatment strategy that would normally rely on a single chemotherapeutic for efficacy. In addition, this work substantiates the use of rifampicin derivatives as a platform for the development of novel treatments to other bacterial agents in addition to tularaemia.
Significantly, TPR1 demonstrated efficacy when delivered alone and in combination with doxycycline, which provides compelling evidence of a superior treatment strategy that would normally rely on a single chemotherapeutic for efficacy. In addition, this work substantiates the use of rifampicin derivatives as a platform for the development of novel treatments to other bacterial agents in addition to tularaemia.
To report
serotyping and susceptibility data from a recent clinical trial (ML-3341-306) comparing delafloxacin with moxifloxacin in the treatment of adults with community-acquired bacterial pneumonia (CABP).

Serotyping and susceptibility testing were conducted on 142 baseline
isolates recovered from subjects participating in a CABP clinical trial.

Overall, 113/142 (79.6%) isolates were vaccine serotypes. 76.8% (109/142) of serotyped isolates were PPSV23 serotypes and 59.9% (85/142) of isolates were PCV13 serotypes. Epigenetic Reader Do inhibitor 15.5% (22/142) of serotyped isolates were serotypes not covered by either vaccine; 4.9% (7/142) of tested isolates were non-typeable. The most common serotypes were serotypes 3 (19.0%; 27/142), 19F (9.9%; 14/142) and 23F (7.0%; 10/142). All of the 142 isolates were susceptible to delafloxacin and moxifloxacin, 76.1% were susceptible to azithromycin and 71.8% were susceptible to penicillin. Multidrug resistance was found among 19A (4/5; 80%), 6A (1/4; 25%), 6B (1/4; 25%), 14 (1/4; 25%), 19F (1/14; 7.1%), and 23F serotypes (2/10; 20%), and among non-typeable
isolates (1/7; 14.3%).

vaccine-targeted serotypes were the main cause of CABP in this Phase 3 CABP study. Fluoroquinolones including delafloxacin remain a good treatment option for CABP in adults caused by
.
S. pneumoniae vaccine-targeted serotypes were the main cause of CABP in this Phase 3 CABP study. Fluoroquinolones including delafloxacin remain a good treatment option for CABP in adults caused by S. pneumoniae.
HIV drug resistance (HIV-DR) is rising in sub-Saharan Africa in both ART-naive and ART-experienced patients.

To estimate the level of acquired DR (ADR) and pre-treatment DR (PDR) across selected urban and rural sites in Southern Africa, in Mozambique.

We conducted two cross-sectional surveys among adult HIV patients (October 2017-18) assessing ADR and PDR. In the (ADR) survey, those on NNRTI-based first-line ART for ≥6 months were recruited (three sites). In the PDR survey, those ART-naive or experienced with ≥3 months of treatment interruption prior were enrolled (eight sites).

Among 1113 ADR survey participants 83% were receiving tenofovir (TDF)/lamivudine (3TC)/efavirenz (EFV). The median time on ART was 4.5 years (Maputo) and 3.2 years (Tete), 8.3% (95% CI 6.2%-10.6%, Maputo) and 15.5% (Tete) had a VL ≥ 1000 copies/mL, among whom 66% and 76.4% had NNRTI+NRTI resistance, and 52.8% and 66.7% had 3TC+TDF-DR. Among those on TDF regimens, 31.1% (Maputo) and 42.2% (Tete) were still TDF susceptible, whernsideration.
Antibiotic use requires regular monitoring to prevent emergence of antibiotic resistance.

To assess antibiotic prescribing patterns at health care facilities (HCF) in Ilala district, Tanzania.

A 1 year retrospective study was conducted in four HCFs using WHO/International Network of Rational Use of Drugs (INRUD) core prescribing indicators. Factors associated with antibiotic prescription were analysed using logistic regression model.

A total of 604 prescriptions were reviewed. Patients had median age (IQR) of 15 (4-31) years with majority having upper respiratory tract infection 33.3% (
201), urinary tract infection 31.1% (
188) or diarrhoea 21.2% (
128). Out of 624 prescribed antibiotics, amoxicillin was the most common (22.7%), followed by ciprofloxacin (13.6%) and metronidazole (11.6%). The studied HCFs had an average of 1.99 medicines prescribed per consultation (reference 1.6-1.8). Of 1203 medicines prescribed, 51.9% (
624) were antibiotics (reference 20.0%-26.8%). Additionally, 97.6% (
609) of the antibiotics appeared on the national essential medicines list, whereby 84.4% (
510) were prescribed by generic names (reference 100%). Patients with peptic ulcers had a 4.4-fold higher chance of receiving antibiotics [adjusted odds ratio (aOR)
4.4, 95% CI = 1.918-10.13,
0.0001] while patients with diarrhoea had a 2.6-fold higher chance of receiving at least one antibiotic (aOR = 2.6, 95% CI = 1.206-5.491,
0.015).

We found inappropriate use of antibiotics in the studied primary HCFs. Antibiotic stewardship programmes should be extended to primary HCFs found in Ilala district.
We found inappropriate use of antibiotics in the studied primary HCFs. Antibiotic stewardship programmes should be extended to primary HCFs found in Ilala district.
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