Marie-Christine Payen

Clinical use of the meropenem-clavulanate combination for extensively drug-resistant tuberculosis.

Mycobacterium tuberculosis strains resistant to almost all available anti-tuberculosis drugs are an increasing threat to public health worldwide. Among existing drugs with potential antimycobacterial effects, the combination of meropenem with clavulanate has been shown to have potent in vitro bactericidal activity against extensively drug-resistant tuberculosis (XDR-TB). To explore its potential clinical efficacy, a meropenem-clavulanate-containing salvage regimen was started in six patients with severe pulmonary XDR-TB, in association with the only one or two remaining active second-line drugs. Encouraging preliminary data are detailed and discussed.Mycobacterium tuberculosis strains resistant to almost all available anti-tuberculosis drugs are an increasing threat to public health worldwide. Among existing drugs with potential antimycobacterial effects, the combination of meropenem with clavulanate has been shown to have potent in vitro bactericidal activity against extensively drug-resistant tuberculosis (XDR-TB). To explore its potential clinical efficacy, a meropenem-clavulanate-containing salvage regimen was started in six patients with severe pulmonary XDR-TB, in association with the only one or two remaining active second-line drugs. Encouraging preliminary data are detailed and discussed.

Meropenem/clavulanate and linezolid treatment for extensively drug-resistant tuberculosis.

The combination of meropenem with clavulanate has high antimycobacterial activity in vitro against extensively drug-resistant Mycobacterium tuberculosis strains. We report the successful use of this combination in association with linezolid in the management of an advanced extensively drug-resistant tuberculosis disease with complex second-line drug resistance in a 14-year-old teenager.

A controlled trial of dapsone versus pyrimethamine-sulfadoxine for primary prophylaxis of Pneumocystis carinii pneumonia and toxoplasmosis in patients with AIDS

Pneumocystis carinii pneumonia (PCP) is the most common opportunistic human immunodeficiency virus (HIV)-related infection, occurring in 85% of HIV infected patients without prophylaxis. Preventive treatment is required when CD4 cell count falls below 200 cells per cubic millimeter. Cotrimoxazole has been shown to be highly effective but alternative drug regimens are often necessary because of the frequent drug hypersensitivity exhibited by HIV infected patients. The aim of this prospective, open, randomized, one-site study, involving HIV-infected patients with a CD4 cell count below 200/mm3, or a percentage under 20%, randomly assigned to receive either dapsone 50 mg daily or Fansidar one tablet weekly, was to compare the efficacy and safety of these drugs in the primary prophylaxis of PCP. Both dapsone and Fansidar appear to be safe and effective alternative agents for the prevention of PCP. Their role in Toxoplasma gondii prophylaxis requires further evaluation.

EPIDEMIOLOGY OF MDR-TB IN A BELGIAN INFECTIOUS DISEASES UNIT: A 15 YEARS REVIEW

Abstract Introduction: For the last 20 years the world has seen the emergence of a growing epidemic of MDR-TB, followed by the appearance of XDR-TB. Both require longer, more expensive and more toxic treatments. MDR-TB and especially XDR-TB are associated with a lower cure rate than non MDR-TB. Materials and Methods: We reviewed retrospectively all cases of MDR-and XDR-TB managed at St Pierre University Hospital between 1996 and 2010. Epidemiological, clinical, bacteriological, treatment, follow up and outcome were collected and analysed. Results: We recorded 73 instances of MDR-TB and 11 XDR-TB for a total of 78 patients. All but 4 patients were of non Belgian origin. 10 patients were co-infected with HIV. A median of 4 active drugs (1-5) were used for a median of 448 days (329-616). 41 MDR-TB (56%) and 1 XDR-TB (1%) were considered as cured and 20 are still on treatment. Since 2007, increasing resistance to second line injectable drugs, fluoroquinolones and even linezolid (1 case) is observed. Extensive resistance was mainly found in patients who had previously been mismanaged with second line agents. Conclusions: This study illustrates the growing epidemic of MDR and XDR-TB, it emphasizes the importance of proper diagnosis and adequate management of TB in patients at risk for resistance and stresses the need for new therapies.

Meropenem-clavulanate for drug-resistant tuberculosis: a follow-up of relapse-free cases

BACKGROUND Extensively drug-resistant tuberculosis (XDR-TB), defined as TB caused by a Mycobacterium strain resistant to at least rifampicin, isoniazid, any fluoroquinolone and one of the injectable anti-tuberculosis drugs, remains a worldwide public health threat. Among repurposed drugs empirically used for XDR-TB cases, carbapenems have been studied in vitro and in animal models, with encouraging results. However, only short-term follow-up data from clinical studies are currently available. OBJECTIVES To study the long-term follow-up of XDR-TB cases treated with a regimen containing meropenem-clavulanate (M/Clav). DESIGN Retrospective observational case series study at a single hospital. METHODS All hospitalised drug-resistant TB patients who received M/Clav as part of their treatment from 2009 to 2016 were included. Demographic and clinical data were extracted from medical records. RESULTS Eighteen XDR-TB patients were included in the analysis. The successful outcome and mortality rates were respectively 83.3% and 11.1%. No relapses were observed in cured patients after a median follow-up of 4 years. No specific adverse events were attributed to treatment with M/Clav. CONCLUSION The rate of sustained successful treatment outcome observed here is far higher than the 26% observed in the 2014 World Health Organization XDR-TB cohort, suggesting that carbapenems may be beneficial for the treatment of difficult-to-treat TB cases.

Immune Activation by Mycobacterium tuberculosis in HIV-Infected and -Uninfected Subjects.

Introduction: This study investigates the influence of Mycobacterium tuberculosis infection on immune activation biomarkers, both in HIV-infected and -uninfected subjects. Methods: Forty-eight treatment-naive HIV-infected patients and 74 HIV-uninfected subjects were recruited and divided into groups according to their M. tuberculosis infection status: latent tuberculosis infection (LTBI), active tuberculosis (TB), and no evidence of M. tuberculosis infection. The expression of cellular markers CD38 and HLA-DR on circulating CD8+ T lymphocytes and the plasmatic levels of soluble markers interleukin-6, sCD14, and D-Dimer were measured and compared between groups. The HIV-infected patients with no evidence of M. tuberculosis or with LTBI who initiated antiretroviral treatment were tested again for these biomarkers once viral suppression was reached. Results: In both HIV-infected and -uninfected groups, patients with TB had higher levels of immune activation markers than subjects with LTBI and with no evidence of M. tuberculosis. Among the HIV-uninfected subjects, no significant difference in biomarker level was found between those presenting LTBI and those with no evidence of M. tuberculosis. The effect of LTBI on activation biomarkers in the HIV-infected groups was inconclusive because of the small number of individuals in the HIV+/LTBI group. sCD14 and D-Dimer levels were significantly higher in the TB-only group than in the HIV-only group. Discussion: Although TB is associated with an increase in biomarkers of immune activation, the effect of LTBI is less evident. Further investigation is warranted, and according to our results, soluble markers may offer greater sensitivity for the evaluation of M. tuberculosis–associated immune activation than cellular markers.

Dolutegravir as a trigger for DRESS syndrome

Dolutegravir is an increasingly-used second-generation human immunodeficiency virus integrase strand transfer inhibitor. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome has been described in several patients treated with raltegravir but to our knowledge, there is no previous report of DRESS syndrome associated with dolutegravir.

Renal Fanconi syndrome with meropenem-containing regimen in drug-resistant tuberculosis

We read with great interest the correspondence by Abadie et al. [1] describing the case of extensively drug-resistant tuberculosis patient developing renal Fanconi syndrome while receiving a meropenem/amoxicillin–clavulanate-containing regimen. Renal Fanconi syndrome reported as rare adverse event during treatment of XDR-TB with meropenem http://ow.ly/3RHG30hVsef

Isolation unit for multidrug-resistant tuberculosis patients in a low endemic country, a step towards the World Health Organization End TB Strategy

Tuberculosis (TB) remains a threat to public health and is the second cause of death due to a single infectious agent after HIV/AIDS. The worldwide distribution of TB is heterogeneous. The incidence is decreasing in most high-income regions, but the situation remains worrying in many parts of the world. The emergence of Mycobacterium tuberculosis strains resistant to key agents used in treatment (rifampin and isoniazid) contributes to TB transmission around the world. To achieve TB elimination, both high and low endemic countries must upscale their efforts to decrease disease transmission and improve cure rates. Management of drug-resistant TB is of particular importance. In this paper, we discuss the different models of care of multidrug-resistant TB (MDR-TB), the ethical considerations and the specific constraints present in high income countries. The management model chosen by the Belgian TB specialists in accordance with public health authorities as well as building of a specific MDR/XDR-TB isolation unit are also discussed.

Is systematic screening and treatment for latent tuberculosis infection in HIV patients useful in a low endemic setting

Objectives: A decreasing incidence of tuberculosis (TB) among HIV patients has been documented in high-income settings and screening for tuberculosis is not systematically performed in many clinics (such as ours). Our objectives are to evaluate whether a same decline of incidence was seen in our Belgian tertiary center and to evaluate whether systematic screening and prophylaxis of tuberculosis should remain part of routine practice. Methods: Between 2005 and 2012, the annual incidence of tuberculosis among adult HIV patients was measured. The impact of demographic characteristics and CD4 nadir on the incidence of active TB was evaluated. Results: Among the 1167 patients who entered the cohort, 42 developed active TB with a significant decrease of annual incidence from 28/1000 patient-years in 2005 to 3/1000 patient-years in 2012. Among the 42 cases, 83% were of sub-Saharan origin. Median CD4 cell count upon HIV diagnosis was significantly lower in TB cases and 60% had a nadir CD4 below 200/μl. Thirty-six percent of incident TB occurred within 14 days after HIV diagnosis. Conclusion: A significant decline of TB incidence in HIV patients was observed. Incident TB occurred mainly in African patients, with low CD4 upon HIV diagnosis. A significant proportion of TB cases were discovered early in follow-up which probably reflects TB already present upon HIV diagnosis. In a low endemic setting, exclusion of active TB upon HIV diagnosis remains a priority and screening for LTBI should focus on HIV patients from high risk groups such as migrants from endemic regions, especially in patients with low CD4 nadir.