Poor performance of paired tests of latent tuberculosis in highly immune-compromised individuals exposed to multidrug-resistant tuberculosis: time for new diagnostic markers.

Guideline-based recommendations for diagnosis of latent TB in highly immune suppressed populations are difficult to interpret and poorly characterised. More accurate biomarkers independent of T-cell functions are urgently required. https://bit.ly/41P8vTa.

Management of isoniazid-monoresistant tuberculosis (Hr-TB) in Queensland, Australia: a retrospective case series.

OBJECTIVES: Drug-resistance represents a major threat in the fight against tuberculosis. Globally, isoniazid-monoresistant tuberculosis (Hr-TB) is twice as common as multidrug/rifampicin-resistant (MDR/RR)-TB. Recently updated WHO guidelines now recommend treatment of Hr-TB with rifampicin, ethambutol, pyrazinamide and levofloxacin for at least six months. Our primary objective was to define the frequency, treatment and outcomes for Hr-TB in Queensland, Australia. We also sought to determine the frequency of fluoroquinolone use and whether its inclusion improved outcomes. METHODS: Retrospective case series of tuberculosis notifications in Queensland between 2000 and 2017 with at least low-level isoniazid resistance and preserved susceptibility to other first-line oral agents. RESULTS: Hr-TB was identified in 7.2% of all notifications. Where outcomes were assessable (163/198), 76.1% were treated with first-line agents only and 11.0% received at least six months of a fluoroquinolone-containing regimen (consistent with recent WHO guidelines). Favourable outcomes were achieved in 95.7%, comparable to fully susceptible disease (94.9%). Inclusion of a fluoroquinolone did not significantly improve outcomes compared with a regimen containing first-line agents only, although these cases were more likely to have high-level resistance. Previous treatment made an unfavourable outcome more likely. CONCLUSIONS: Hr-TB is prevalent in Queensland. Treatment outcomes in our cohort were comparable to fully susceptible disease. The current WHO-recommended regimen did not confer advantage over an appropriately constructed regimen containing first-line agents only. Our findings suggest that, in a well-resourced setting with good programmatic management, the addition of a fluoroquinolone may not substantially improve outcomes - potentially allowing these agents to be reserved for more extensively resistant disease.

Prospective evaluation of improving fluoroquinolone exposure using centralised therapeutic drug monitoring (TDM) in patients with tuberculosis (PERFECT): a study protocol of a prospective multicentre cohort study.

INTRODUCTION: Global multidrug-resistant tuberculosis (MDR-TB) treatment success rates remain suboptimal. Highly active WHO group A drugs moxifloxacin and levofloxacin show intraindividual and interindividual pharmacokinetic variability which can cause low drug exposure. Therefore, therapeutic drug monitoring (TDM) of fluoroquinolones is recommended to personalise the drug dosage, aiming to prevent the development of drug resistance and optimise treatment. However, TDM is considered laborious and expensive, and the clinical benefit in MDR-TB has not been extensively studied. This observational multicentre study aims to determine the feasibility of centralised TDM and to investigate the impact of fluoroquinolone TDM on sputum conversion rates in patients with MDR-TB compared with historical controls. METHODS AND ANALYSIS: Patients aged 18 years or older with sputum smear and culture-positive pulmonary MDR-TB will be eligible for inclusion. Patients receiving TDM using a limited sampling strategy (t=0 and t=5 hours) will be matched to historical controls without TDM in a 1:2 ratio. Sample analysis and dosing advice will be performed in a centralised laboratory. Centralised TDM will be considered feasible if >80% of the dosing recommendations are returned within 7 days after sampling and 100% within 14 days. The number of patients who are sputum smear and culture-negative after 2 months of treatment will be determined in the prospective TDM group and will be compared with the control group without TDM to determine the impact of TDM. ETHICS AND DISSEMINATION: Ethical clearance was obtained by the ethical review committees of the 10 participating hospitals according to local procedures or is pending (online supplementary file 1). Patients will be included after obtaining written informed consent. We aim to publish the study results in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03409315).

The clinical significance of Mycobacterium triplex.

OBJECTIVES: Mycobacterium triplex is a slow-growing nontuberculous mycobacteria (NTM) and is a rare cause of human disease. The pathogenicity, natural history and spectrum of disease is unknown. The aim of this study was to review the clinical features, outcomes and drug susceptibility testing (DST) of all M. triplex isolates in Queensland, Australia to guide management of this rare NTM infection in the future. METHODS: This retrospective study included all patients who isolated M. triplex in Queensland, Australia from the 1st January 2000 to 31st December 2016. Clinical information was obtained from medical records to determine the clinical significance of isolates, natural history of disease and treatment outcomes. DST was performed on 15 isolates. RESULTS: Forty-three patients (21 male) had positive cultures for M. triplex. Thirty-nine patients had isolates from pulmonary specimens and 17 (43.6%) met the American Thoracic Society criteria for NTM lung disease. Six patients with pulmonary infection received antimicrobial therapy with 5 patients demonstrating treatment success. Four patients had localised extrapulmonary disease and were cured with surgical management ±â€¯antimicrobial therapy. DST suggests 93% of isolates are susceptible to macrolides. CONCLUSION: This is the largest case series of M. triplex isolates and confirms it is a rare human pathogen. Extrapulmonary disease responded well to surgical management. Treatment of M. triplex pulmonary disease is challenging, and the optimal antimicrobial regimen is unknown. However, the DST data suggests macrolide resistance is rare and macrolides should be included in treatment regimens.

M ycobacterium abscessus pulmonary disease: individual patient data meta-analysis.

Treatment of Mycobacterium abscessus pulmonary disease (MAB-PD), caused by M. abscessus subsp. abscessus, M. abscessus subsp. massiliense or M. abscessus subsp. bolletii, is challenging.We conducted an individual patient data meta-analysis based on studies reporting treatment outcomes for MAB-PD to clarify treatment outcomes for MAB-PD and the impact of each drug on treatment outcomes. Treatment success was defined as culture conversion for ≥12 months while on treatment or sustained culture conversion without relapse until the end of treatment.Among 14 eligible studies, datasets from eight studies were provided and a total of 303 patients with MAB-PD were included in the analysis. The treatment success rate across all patients with MAB-PD was 45.6%. The specific treatment success rates were 33.0% for M. abscessus subsp. abscessus and 56.7% for M. abscessus subsp. massiliense For MAB-PD overall, the use of imipenem was associated with treatment success (adjusted odds ratio (aOR) 2.65, 95% CI 1.36-5.10). For patients with M. abscessus subsp. abscessus, the use of azithromycin (aOR 3.29, 95% CI 1.26-8.62), parenteral amikacin (aOR 1.44, 95% CI 1.05-1.99) or imipenem (aOR 7.96, 95% CI 1.52-41.6) was related to treatment success. For patients with M. abscessus subsp. massiliense, the choice among these drugs was not associated with treatment outcomes.Treatment outcomes for MAB-PD are unsatisfactory. The use of azithromycin, amikacin or imipenem was associated with better outcomes for patients with M. abscessus subsp. abscessus.

Pleuropulmonary tuberculosis with spinal lesions due to metastatic malignancy differentiated definitively on imaging.

A healthy 31-year-old man presenting with back pain was found to have multiple spinal enhancing lesions on MRI. An incidental asymptomatic large pleural effusion was identified on investigations for the back pain and pleural and pulmonary tuberculosis (TB) was subsequently diagnosed. The radiographical features on MRI spine were not typical of spinal TB and a Ga68 DOTATATE Positron Emission Tomography (PET)/CT confirmed metastatic paraganglioma with multiple bone metastases. Although metastatic paraganglioma is rare, this case highlights that even in young patients dual pathology needs to be considered. Most importantly, it is a reminder to physicians managing TB of the clues that help distinguish spinal TB from important alternative causes, including metastatic malignancy.

Management of rifampicin mono-resistant tuberculosis in Queensland, Australia: a retrospective case series.

Rifampicin mono-resistant tuberculosis (RMR-TB) is rare worldwide; however, it is associated with poor treatment outcomes. Evidence to guide the treatment of RMR-TB is lacking. International guidelines have recently changed and now recommend that RMR-TB should be managed with multi-drug-resistant tuberculosis (MDR-TB) regimens. This report is a retrospective review of all cases of RMR-TB in Queensland, Australia, from 2000 to 2016 to assess treatment outcomes and regimens used. Twelve cases of RMR-TB were diagnosed, with seven patients completing treatment in Queensland. This study confirms that RMR-TB is rare in Queensland. Generally extended regimens with first-line agents +/- a fluoroquinolone were used, and all patients who completed treatment in Queensland had successful outcomes.

Mycobacterium shimoidei, a Rare Pulmonary Pathogen, Queensland, Australia.

Nontuberculous mycobacteria are human pathogens with increasing incidence and prevalence worldwide. Mycobacterium shimoidei is a rare cause of pulmonary disease, with only 15 cases previously reported. This series documents an additional 23 cases of M. shimoidei from Queensland, Australia, and highlights the pathogenicity and clinical role of this species.

Safety of IV amikacin in the treatment of pulmonary non-tuberculous mycobacterial disease.

BACKGROUND AND OBJECTIVE: Pulmonary non-tuberculous mycobacterial (NTM) disease has a high mortality rate and often requires treatment with intravenous amikacin. We report on safety data in patients treated with intravenous amikacin for pulmonary. METHODS: A retrospective observational study (2002-2012) was performed including 45 patients that met American Thoracic Society criteria for pulmonary NTM disease and were treated with intravenous amikacin at three hospitals in Brisbane, Australia. The aim was to define the rates of common adverse effects, the patient and regimen factors associated with these adverse effects and describe the rates of treatment success and associated factors. RESULTS: Forty-five patients (34 women; median age 63 years) were treated for Mycobacterium intracellulare (25), Mycobacterium abscessus (13), Mycobacterium avium (6) and Mycobacterium fortuitum (1) using multi-drug therapy that included IV amikacin. Transient ototoxicity was seen in eight (18%) but long-term ototoxicity was seen in only three (7%). There were no cases of nephrotoxicity and no long-term vestibulotoxicity. Sustained culture conversion at 6 months was only found in 17 (38%), however, the majority (34 patients, 76%) had a clinical response to treatment determined by an improvement in symptoms. CONCLUSION: Carefully selected and closely monitored patients with pulmonary NTM can be treated using IV amikacin safely with low rates of toxicity. No pretreatment patient or regimen factors were predictive of toxicity or treatment success in this small cohort. Lower treatment success rates were found than previous trials suggest there is a difficult balance in this patient group between treatment success and toxicities.