Levofloxacin pharmacokinetics in saliva as measured by a mobile microvolume UV spectrophotometer among people treated for rifampicin-resistant TB in Tanzania.

BACKGROUND: Early detection and correction of low fluoroquinolone exposure may improve treatment of MDR-TB. OBJECTIVES: To explore a recently developed portable, battery-powered, UV spectrophotometer for measuring levofloxacin in saliva of people treated for MDR-TB. METHODS: Patients treated with levofloxacin as part of a regimen for MDR-TB in Northern Tanzania had serum and saliva collected concurrently at 1 and 4 h after 2 weeks of observed levofloxacin administration. Saliva levofloxacin concentrations were quantified in the field via spectrophotometry, while serum was analysed at a regional laboratory using HPLC. A Bayesian population pharmacokinetics model was used to estimate the area under the concentration-time curve (AUC0-24). Subtarget exposures of levofloxacin were defined by serum AUC0-24 <80 mg·h/L. The study was registered at Clinicaltrials.gov with clinical trial identifier NCT04124055. RESULTS: Among 45 patients, 11 (25.6%) were women and 16 (37.2%) were living with HIV. Median AUC0-24 in serum was 140 (IQR = 102.4-179.09) mg·h/L and median AUC0-24 in saliva was 97.10 (IQR = 74.80-121.10) mg·h/L. A positive linear correlation was observed with serum and saliva AUC0-24, and a receiver operating characteristic curve constructed to detect serum AUC0-24 below 80 mg·h/L demonstrated excellent prediction [AUC 0.80 (95% CI = 0.62-0.94)]. Utilizing a saliva AUC0-24 cut-off of 91.6 mg·h/L, the assay was 88.9% sensitive and 69.4% specific in detecting subtarget serum AUC0-24 values, including identifying eight of nine patients below target. CONCLUSIONS: Portable UV spectrophotometry as a point-of-care screen for subtarget levofloxacin exposure was feasible. Use for triage to other investigation or personalized dosing strategy should be tested in a randomized study.

TB or not TB? Definitive determination of species within the Mycobacterium tuberculosis complex in unprocessed sputum from adults with presumed multidrug-resistant tuberculosis.

OBJECTIVES: Differences among Mycobacterium tuberculosis complex (MTC) species may predict drug resistance or treatment success. Thus, we optimised and deployed the genotype MTBC assay (gMTBC) to identify MTC to the species level, and then performed comparative genotypic drug-susceptibility testing to anti-tuberculosis drugs from direct sputum of patients with presumed multidrug-resistant tuberculosis (MDR-TB) by the MTBDRplus/sl reference method. METHODS: Patients with positive Xpert® MTB/RIF (Xpert) results were consented to provide early-morning-sputum for testing by the gMTBC and the reference MTBDRplus/sl. Chi-square or Fisher's exact test compared proportions. Modified Poisson regression modelled detection of MTC by gMTBC. RESULTS: Among 73 patients, 53 (73%) were male and had a mean age of 43 (95% CI; 40-45) years. In total, 34 (47%), 36 (49%) and 38 (55%) had positive gMTBC, culture and MTBDR respectively. Forty patients (55%) had low quantity MTC by Xpert, including 31 (78%) with a negative culture. gMTBC was more likely to be positive in patients with chest cavity 4.18 (1.31-13.32, P = 0.016), high-quantity MTC by Xpert 3.03 (1.35-6.82, P = 0.007) and sputum smear positivity 1.93 (1.19-3.14, P = 0.008). The accuracy of gMTBC in detecting MTC was 95% (95% CI; 86-98; κ = 0.89) compared to MTBDRplus/sl. All M. tuberculosis/canettii identified by gMTB were susceptible to fluoroquinolone and aminoglycosides/capreomycin. CONCLUSIONS: The concordance between the gMTBC assay and MTBDRplus/sl in detecting MTC was high but lagged behind the yield of Xpert MTB/RIF. All M. tuberculosis/canettii were susceptible to fluoroquinolones, a core drug in MDR-TB treatment regimens.

Do reflex comments on laboratory reports alter patient management?

INTRODUCTION: Laboratory comments appended on clinical biochemistry reports are common in the UK. Although popular with clinicians and the public, there is little evidence that these comments influence the clinical management of patients. METHODS: We provided reflex automated laboratory comments on all primary care lipid results including, if appropriate, recommendation of direct referral to the West Midlands Familial Hypercholesterolaemia service (WMFHS). Over a two-year period, the number GP referrals from the Wolverhampton City Clinical Commissioning Group (CCG) to the WMFHS were compared with four comparator CCGs of similar population size, who were not provided with reflex laboratory comments. RESULTS: Over the study period, the WMFHS received more referrals from Wolverhampton GPs (241) than any other comparator CCG (range 8-65) and greater than the combined referrals (172) from all four comparator CCGs. CONCLUSION: Targeted reflex laboratory comments may influence the clinical management of patients and may have a role in the identification of individuals with familial hypercholesterolaemia.

Meta-narrative review of molecular methods for diagnosis and monitoring of multidrug-resistant tuberculosis treatment in adults.

Early and accurate diagnosis and rigorous clinical and microbiological monitoring of multidrug-resistant tuberculosis (MDR-TB) treatment can curb morbidity and mortality. While others are still under evaluation, the World Health Organization has recommended few novel molecular methods for MDR-TB diagnosis only. We present current molecular methods for diagnosis and monitoring of MDR-TB treatment in TB-endemic settings. A systematic meta-narrative review was conducted according to the RAMESES recommendations. Electronic databases were searched for relevant articles published in English language from January 2013 to June 2018. Based on predefined criteria, two independent reviewers extracted the key messages from relevant articles. Disagreement between them was resolved through discussion and the involvement of a third reviewer, if needed. Key messages were synthesized to create the meta-narratives for method's accuracy, drug-susceptibility capability, and laboratory infrastructure required. We included 33 articles out of 1213 records retrieved, of which 16 (48%) and 12 (36%) were conducted in high- and low-TB-endemic settings, respectively. Xpert® MTB/RIF, GenoType MTBDRplus, GenoType MTBDRsl, FlouroType™ MTBDR, TB TaqMan® array card, and DNA sequencers can accurately guide effective treatment regimens. Molecular bacterial load assay quantifies mycobactericidal impact of these regimens. Although they present inherent advantages compared to the current standard of care, they carry important limitations to implementation and/or scale-up. Therefore, considerable effort must now be directed to implementation and health systems research to maximize these forecasted benefits for individual patient's health outcomes.

Radiographic Assessment of the Quality of Root Canal Fillings Performed by Senior Dental Students.

OBJECTIVE: To evaluate the radiographic technical quality of root canal fillings performed by senior dental students at Alfarabi colleges for dentistry, Kingdom of Saudi Arabia. METHODS: Radiographic assessment was conducted for 246 teeth (390 root canals) endodontically treated by senior dental students to evaluate the quality of root canal fillings. Three criteria were evaluated to assess the technical quality of root canal fillings: length, density, and taper. The root canal filling was considered acceptable if it had an adequate length with no voids and consistent taper from the orifice to the apex. Statistical analysis was conducted using Kruskal-Wallis, Mann-Whitney, and chi-square tests (P=0.05). RESULTS: Acceptable root canal fillings were detected in 127 (32.6%) patients. The frequency of an acceptable root canal filling was the highest for the upper anterior teeth (40%). There were significant differences in the length and density among the types of teeth (P<0.05). However, there was no significant difference in the taper among the types of teeth (P>0.05). CONCLUSION: The quality of root canal fillings performed by senior undergraduate dental students at AlFarabi colleges for dentistry was acceptable in 32.6% of patients. This outcome enhanced the poor performance of undergraduate dental students in the area of endodontics.

Quality improvement for HIV screening in a primary care resident clinic.

Primary care physicians are responsible for the initiation of the preventive health screening tests and examinations for their patients. Resident physicians may be uncomfortable obtaining a sexual history from their patient. A performance improvement project was carried out in the resident clinic to see if we could improve HIV screening of our patients. With a cohesive effort between the faculty preceptors and residents, we were able to improve screening rates for HIV and improve some aspects, but not all, of sexual history taking for our population of patients. We identified two patients who screened positive for a rate of 1.4%. ABBREVIATIONS: CDC.