Recent innovations and new applications of outpatient parenteral antimicrobial therapy.

INTRODUCTION: Outpatient parenteral antimicrobial therapy (OPAT) is safe and effective for selected patients managed within an organized clinical service. Service configurations however are evolving, patient populations are changing and new evidence is emerging which challenges traditional OPAT practice. AREAS COVERED: This review will discuss evolving OPAT service delivery from the traditional model of infusion center toward nonspecialist, community and remotely delivered OPAT and the challenges this represents. We consider new patient populations including those with incurable infection or infections at the end of life and difficult to reach populations including people who inject drugs. The evidence base that underpins the multi-disciplinary approach to OPAT delivery will be examined and particularly the role of the antimicrobial pharmacist and specialist nurse. Evidence for new treatment options which challenge established OPAT practice including complex oral antibiotic regimens, long acting parenteral agents and drug stability in continuous infusion antibiotics will be considered. Finally we emphasize the central importance of antimicrobial stewardship and good clinical governance which should underpin OPAT practice. EXPERT OPINION: Changing patient populations, service structures and team roles coupled with a growing infection management evidence base means that OPAT services and practice must evolve. Challenging traditional practice is essential to ensure best patient outcomes and cost-efficiency.

Tuberculosis bacillary load, an early marker of disease severity: the utility of tuberculosis Molecular Bacterial Load Assay.

In this comparative biomarker study, we analysed 1768 serial sputum samples from 178 patients at 4 sites in Southeast Africa. We show that tuberculosis Molecular Bacterial Load Assay (TB-MBLA) reduces time-to-TB-bacillary-load-result from days/weeks by culture to hours and detects early patient treatment response. By day 14 of treatment, 5% of patients had cleared bacillary load to zero, rising to 58% by 12th week of treatment. Fall in bacillary load correlated with mycobacterial growth indicator tube culture time-to-positivity (Spearmans r=-0.51, 95% CI (-0.56 to -0.46), p<0.0001). Patients with high pretreatment bacillary burdens (above the cohort bacillary load average of 5.5log10eCFU/ml) were less likely to convert-to-negative by 8th week of treatment than those with a low burden (below cohort bacillary load average), p=0.0005, HR 3.1, 95% CI (1.6 to 5.6) irrespective of treatment regimen. TB-MBLA distinguished the bactericidal effect of regimens revealing the moxifloxacin-20 mg rifampicin regimen produced a shorter time to bacillary clearance compared with standard-of-care regimen, p=0.008, HR 2.9, 95% CI (1.3 to 6.7). Our data show that the TB-MBLA could inform clinical decision making in real-time and expedite drug TB clinical trials.