Pretomanid for tuberculosis: a systematic review.

BACKGROUND: Outcomes of treatment of tuberculosis patients with regimens including pretomanid have not yet been systematically reviewed. OBJECTIVES: To appraise existing evidence on efficacy and safety of pretomanid in tuberculosis. DATA SOURCES: Pubmed, clinicaltrials.gov. and Cochrane library. STUDY ELIGIBILITY CRITERIA: Quantitative studies presenting original data on clinical efficacy or safety of pretomanid. PARTICIPANTS: Patients with tuberculosis. INTERVENTIONS: Treatment with pretomanid or pretomanid-containing regimens in minimum one study group. METHODS: Two authors independently extracted data and assessed risk of bias. Data on efficacy (early bactericidal activity, bactericidal activity, end-of-treatment outcomes and acquired resistance) and safety were summarized in tables. Mean differences in efficacy outcomes between regimens across studies were calculated. RESULTS: Eight studies were included; four randomized controlled trials on 2-week early bactericidal activity in rifampicin-susceptible tuberculosis, three trials with randomized rifampicin-susceptible tuberculosis arms and a single rifampicin-resistant tuberculosis arm (two on 8-week bactericidal activity, one on end-of-treatment outcomes), one single-arm trial with end-of-treatment outcomes in highly resistant tuberculosis. Activity of pretomanid-moxifloxacin-pyrazinamide was superior to standard treatment on daily change in colony-forming units at days 0-2, 0-56 and 7-56 and time to culture conversion in rifampicin-susceptible tuberculosis (hazard ratio: 1.7; 95% CI 1.1-2.7), but not at end of treatment in one study. This study was stopped due to serious hepatotoxic adverse events, including three deaths, in 4% (95% CI 2-8) patients on pretomanid-moxifloxacin-pyrazinamide and none in controls. In patients with uncomplicated rifampicin-resistant tuberculosis on pretomanid-moxifloxacin-pyrazinamide treatment, 91% (95% CI 59-100) had favourable end-of-treatment outcomes. In patients with highly resistant tuberculosis, 90% (95% CI 83-95) on pretomanid-bedaquiline-linezolid had favourable outcomes six months after treatment, but linezolid-related toxicity was frequent. No acquired resistance to pretomanid was reported. CONCLUSIONS: Evidence suggests an important role for pretomanid in rifampicin-resistant and highly resistant tuberculosis. Trials comparing pretomanid to existing core and companion drugs are needed to further define that role.

How to bring residents' psychosocial well-being to the heart of the fight against Covid-19 in Belgian nursing homes-A qualitative study.

BACKGROUND: Nursing homes (NH) for the elderly have been particularly affected by the Covid-19 pandemic mainly due to their hosted vulnerable populations and poor outbreak preparedness. In Belgium, the medical humanitarian organization Médecins Sans Frontières (MSF) implemented a support project for NH including training on infection prevention and control (IPC), (re)-organization of care, and psychosocial support for NH staff. As psychosocial and mental health needs of NH residents in times of Covid-19 are poorly understood and addressed, this study aimed to better understand these needs and how staff could respond accordingly. METHODS: A qualitative study adopting thematic content analysis. Eight focus group discussions with direct caring staff and 56 in-depth interviews with residents were conducted in eight purposively and conveniently selected NHs in Brussels, Belgium, June 2020. RESULTS: NH residents experienced losses of freedom, social life, autonomy, and recreational activities that deprived them of their basic psychological needs. This had a massive impact on their mental well-being expressed in feeling depressed, anxious, and frustrated as well as decreased meaning and quality of life. Staff felt unprepared for the challenges posed by the pandemic; lacking guidelines, personal protective equipment and clarity around organization of care. They were confronted with professional and ethical dilemmas, feeling 'trapped' between IPC and the residents' wellbeing. They witnessed the detrimental effects of the measures imposed on their residents. CONCLUSION: This study revealed the insights of residents' and NH staff at the height of the early Covid-19 pandemic. Clearer outbreak plans, including psychosocial support, could have prevented the aggravated mental health conditions of both residents and staff. A holistic approach is needed in NHs in which tailor-made essential restrictive IPC measures are combined with psychosocial support measures to reduce the impact on residents' mental health impact and to enhance their quality of life.

Comparison of first-line tuberculosis treatment outcomes between previously treated and new patients: a retrospective study in Machakos subcounty, Kenya.

BACKGROUND: Since 2016, patients with rifampicin-susceptible tuberculosis (TB) have been treated with the 6-month first-line regimen, regardless of treatment history. We assessed treatment outcomes of previously treated and new patients in Machakos subcounty, Kenya. METHODS: We performed a retrospective cohort study in patients started on first-line treatment between 2016 and 2017. Firth's logistic regression was used to estimate the effect of previous treatment on having a programmatic adverse outcome (either lost to follow-up, death, failure) and treatment failure vs treatment success (either cure or completion). RESULTS: Of 1024 new and 79 previously treated patients, 88.1% and 74.7% were treated successfully, 6.5% and 7.6% died, 4.2% and 10.1% were lost to follow-up and 1.2% and 7.6% had treatment failure, respectively. Previous treatment predicted having a programmatic adverse outcome (adjusted odds ratio [aOR] 2.4 [95% confidence interval {CI} 1.4 to 4.2]) and treatment failure (aOR 7.3 [95% CI 2.6 to 20.4]) but not mortality. Similar correlations were found in 334 new and previously treated patients with confirmed baseline rifampicin susceptibility. CONCLUSION: Previously treated patients were more at risk of experiencing a poor treatment outcome, mainly lost to follow-up and treatment failure. Adherence support may reduce lost to follow-up. Rifampicin drug susceptibility testing coverage should increase. More robust retreatment regimens may reduce treatment failure.

Initial resistance to companion drugs should not be considered an exclusion criterion for the shorter multidrug-resistant tuberculosis treatment regimen.

OBJECTIVES: We investigated whether companion drug resistance was associated with adverse outcomes of the shorter multidrug-resistant tuberculosis (MDR-TB) treatment regimen in Bangladesh after adjustment for fluoroquinolone resistance. METHODS: MDR-TB/rifampicin-resistant tuberculosis patients registered for treatment with a standardized gatifloxacin-based shorter MDR-TB treatment regimen were selected for the study. Drug resistance was determined by the proportion method, gatifloxacin and isoniazid minimum inhibitory concentration testing for selected isolates, and whole-genome sequencing. RESULTS: Low-level fluoroquinolone resistance and high-level fluoroquinolone resistance were the most important predictors of adverse outcomes, with pyrazinamide resistance having a significant yet lower impact. In patients with fluoroquinolone-/second-line-injectable-susceptible tuberculosis, non-eligibility for the shorter MDR-TB treatment regimen (initial resistance to pyrazinamide, ethionamide, or ethambutol) was not associated with adverse outcome (adjusted odds ratio 1.01; 95% confidence interval 0.4-2.8). Kanamycin resistance was uncommon (1.3%). Increasing levels of resistance to isoniazid predicted treatment failure, also in a subgroup of patients with high-level fluoroquinolone-resistant tuberculosis. CONCLUSIONS: Our results suggest that resistance to companion drugs in the shorter MDR-TB treatment regimen, except kanamycin resistance, is of no clinical importance as long as fluoroquinolone susceptibility is preserved. Hence, contrary to current WHO guidelines, exclusions to the standard regimen are justified only in the case of fluoroquinolone resistance. and possibly kanamycin resistance.

Case Report: Dynamics of Acquired Fluoroquinolone Resistance under Standardized Short-Course Treatment of Multidrug-Resistant Tuberculosis.

We report a case of acquired fluoroquinolone (FQ) resistance under short-course multidrug-resistant tuberculosis (MDR-TB) treatment. The patient was managed at Kabutare hospital, one of the two specialized MDR-TB clinics in Rwanda. A low dose of moxifloxacin was used in the first three critical months. Acquired resistance was identified at the ninth month of treatment, 3 months after stopping kanamycin in a strain initially susceptible only to FQs, kanamycin, and clofazimine. Fluoroquinolone resistance was detected in the same month by deep sequencing as routinely used second-line line probe assay and phenotypic drug susceptibility testing. High-dose FQ, preferably gatifloxacin, should be used to maximize effectiveness.

Knowledge transmission, peer support, behaviour change and satisfaction in post Natal clubs in Khayelitsha, South Africa: a qualitative study.

BACKGROUND: The Post Natal Club (PNC) model assures comprehensive care, including HIV and Maternal and Child Health care, for postpartum women living with HIV and their infants during an 18-month postnatal period. The PNC model was launched in 2016 in Town Two Clinic, a primary health care facility in Khayelitsha, South Africa. This qualitative research study aims to understand how participation in PNCs affected knowledge transmission, peer support, behaviour change and satisfaction with the care provided. METHODS: We conducted ten in-depth interviews; three focus group discussions and participant observation with PNC members, health-care workers and key informants selected through purposive sampling. Seventeen PNC members between 21 and 38 years old, three key informants and seven staff working in PNC participated in the research. All participants were female, except for one of the three key informants who was male. Data was collected until saturation. The data analysis was performed in an inductive way and involved an iterative process, using Nvivo11 software. RESULTS: PNC members acquired knowledge on HIV, ART, adherence, infant feeding, healthy eating habits, follow up tests and treatment for exposed infants. Participants believed that PNC created strong relationships among members and offered an environment conducive to sharing experience and advice. Most interviewees stated that participating in PNC facilitated disclosure of their HIV status, enhanced support network and provided role models. PNC members said that they adapted their behaviour based on advice received in PNCs related to infant feeding, ART adherence, monitoring of symptoms and stimulation of early childhood development. The main benefits were believed to be comprehensive care for mother-infant pairs, time-saving and the peer dynamic. The main challenge from the perspective of key informants was the sustainability of dedicating human resources to PNC. CONCLUSION: The PNC model was believed to improve knowledge acquisition, behaviour change and peer support. Participants, staff and the majority of key informants expressed a high level of satisfaction with the PNC model. Sustainability and finding adequate human resources for PNCs remained challenging. Strategies to improve sustainability may include handing over some PNC tasks to members to increase their sense of ownership.

Delivery of an Ebola Virus-Positive Stillborn Infant in a Rural Community Health Center, Sierra Leone, 2015.

We report the case of an Ebola virus (EBOV) RNA-negative pregnant woman who delivered an EBOV RNA-positive stillborn infant at a community health center in rural Sierra Leone, 1 month after the mother's last possible exposure. The mother was later found to be immunoglobulins M and G positive indicating previous infection. The apparent absence of Ebola symptoms and not recognizing that the woman had previous contact with an Ebola patient led health workers performing the delivery to wear only minimal personal protection, potentially exposing them to a high risk of EBOV infection. This case emphasizes the importance of screening for epidemiological risk factors as well as classic and atypical symptoms of Ebola when caring for pregnant women, even once they have passed the typical time frame for exposure and incubation expected in nonpregnant adults. It also illustrates the need for health-care workers to use appropriate personal protection equipment when caring for pregnant women in an Ebola setting.