Hyperglycaemia and pharmacokinetics of rifampicin/isoniazid among TB-HIV co-infected patients in Kampala, Uganda.

OBJECTIVE: 1) To determine the prevalence of diabetes mellitus and impaired fasting glucose (IFG) in patients with TB and HIV co-infection, and 2) to investigate the effect of fasting plasma glucose (FPG) on rifampicin (RIF) and isoniazid (INH) serum concentrations.DESIGN: Retrospective data analysis of a cohort of HIV-infected adults with newly diagnosed pulmonary TB. Plasma glucose and TB drug levels were obtained at Week 0, 2, 8 and 24 of TB treatment.RESULTS: A total of 107 patients were included in this analysis. Random plasma glucose ≥200 mg/dL was found in 1/53 (2%) participant at Week 0. The prevalence of FPG ≥ 126 mg/dL decreased from 8/41 (20%) at Week 2 to 3/89 (3%) at Week 24. IFG (100-125 mg/dL) was observed in 23/41 (56%) participants at Week 2, and 39/89 (44%) at Week 24. FPG was inversely correlated with lower area under the curve (AUC0-24h) for RIF (c = -0.52; 95%CI -0.84 to -0.21; P = 0.001). FPG was not associated with lower INH AUC0-24h.CONCLUSION: We found a high prevalence of FPG ≥ 126 mg/dL, which decreased significantly during treatment, and a high proportion of IFG at the end of TB treatment. Higher FPG was associated with lower AUC for RIF.

[Treatment of acute and recurrent Clostridium difficile infections : What is new?] / Therapie akuter und rekurrenter Clostridium-difficile-Infektionen : Was gibt es Neues?

The incidence of clostridium difficile infections (CDI) remains on a high level globally. In Germany, the number of severe or even lethal cases continues to increase. The main risk factor for the development of CDI is exposure to broad spectrum antibiotics, which disturb the physiological microbiome and therefore enable colonization with C. difficile. According to the updated US and European guidelines, orally administered vancomycin is the treatment of choice. Fidaxomicin is as effective as vancomycin but has the advantage of a lower rate of recurrence. Furthermore, recent clinical studies were able to demonstrate that significantly fewer recurrences occurred in patients who additionally received the monoclonal antibody bezlotoxumab. In recent years, several new antibiotics with narrow-spectrum acitivity and low intestinal resorption have been developed for the treatment of CDI, including surotomycin, cadazolid, and ridinilazol. Novel toxoid vaccines are expected to become an efficacious tool in the prevention of CDI; however, pivotal clinical trials have so far not been completed.

Anti-TB drug concentrations and drug-associated toxicities among TB/HIV-coinfected patients.

Background: Toxicities due to anti-TB treatment frequently occur among TB/HIV-coinfected patients. Objectives: To determine the association between anti-TB drug concentrations and the occurrence of hepatotoxicity and peripheral neuropathy among TB/HIV-coinfected patients. Methods: TB/HIV-coinfected patients were started on standard dose anti-TB treatment according to WHO guidelines. Anti-TB drug concentrations were measured using HPLC 1, 2 and 4 h after drug intake at 2, 8 and 24 weeks following initiation of TB treatment. Participants were assessed for hepatotoxicity using Division of AIDS toxicity tables and for peripheral neuropathy using clinical assessment of tendon reflexes, vibration sensation or symptoms. Cox regression was used to determine the association between toxicities and drug concentrations. Results: Of the 268 patients enrolled, 58% were male with a median age of 34 years. Participants with no hepatotoxicity or mild, moderate and severe hepatotoxicity had a median C max of 6.57 (IQR 4.83-9.41) µg/mL, 7.39 (IQR 5.10-10.20) µg/mL, 7.00 (IQR 6.05-10.95) µg/mL and 3.86 (IQR 2.81-14.24) µg/mL, respectively. There was no difference in the median C max of rifampicin among those who had hepatotoxicity and those who did not ( P = 0.322). There was no difference in the isoniazid median C max among those who had peripheral neuropathy 2.34 (1.52-3.23) µg/mL and those who did not 2.21 (1.45-3.11) µg/mL ( P = 0.49). Conclusions: There was no association between rifampicin concentrations and hepatotoxicity or isoniazid concentrations and peripheral neuropathy among TB/HIV-coinfected patients.

Challenges in achieving a target international normalized ratio for deep vein thrombosis among HIV-infected patients with tuberculosis: a case series.

BACKGROUND: Tuberculosis (TB) and HIV are among the risk factors for deep vein thrombosis (DVT). There are several challenges in the management of DVT patients with TB-HIV co-infection including drug-drug interactions and non-adherence due to pill burden. METHODS: HIV infected patients starting treatment for TB were identified and followed up two weekly. Cases of DVT were diagnosed with Doppler ultrasound and patients were initiated on oral anticoagulation with warfarin and followed up with repeated INR measurements and warfarin dose adjustment. RESULTS: We describe 7 cases of TB and HIV-infected patients in Uganda diagnosed with DVT and started on anticoagulation therapy. Their median age was 30 (IQR: 27-39) years and 86 % were male. All patients had co-medication with cotrimoxazole, tenofovir, lamivudine and efavirenz and some were on fluconazole. The therapeutic range of the International Normalization Ratio (INR) was difficult to attain and unpredictable with some patients being under-anticoagulated and others over-anticoagulated. The mean Time in Therapeutic Range (TTR) for patients who had all scheduled INR measurements in the first 12 weeks was 33.3 %. Only one patient among those with all the scheduled INR measurements had achieved a therapeutic INR by 2 weeks. Four out of seven (57 %) of the patients had at least one INR above the therapeutic range which required treatment interruption. None of the patients had major bleeding. CONCLUSION: We recommend more frequent monitoring and timely dose adjustment of the INR, as well as studies on alternative strategies for the treatment of DVT in TB-HIV co-infected patients.

'If at first you don't succeed, try again'. Looking beyond the initial results of a failed tuberculosis diagnosis.

We report the outcome of investigations conducted in 73 human immunodeficiency virus (HIV) infected Ugandan adults presumed to have pulmonary tuberculosis (PTB). Following initial investigations, 32 of 73 patients were diagnosed with PTB. Of the remaining 41 patients initially classified as 'non-PTB', six had a delayed PTB diagnosis after a median of 6 weeks. Of the six patients lost to follow-up, four (66%) were reported to have died. Active tracking and close monitoring of HIV-infected patients presumed to have PTB independently of initial investigation results may reduce morbidity and mortality among this vulnerable patient group.

Nous rapportons le résultat d'investigations réalisées chez 73 adultes Ougandais positifs au virus de l'immunodéficience humaine (VIH) et présumés d'avoir une tuberculose pulmonaire (TBP). Après les investigations initiales, 32 de 73 patients ont eu un diagnostic de TBP. Sur les 41 patients restants initialement classés comme « pas de TBP ¼, six ont eu un diagnostic de TBP retardé après un délai médian de 6 semaines. Sur les six patients perdus de vue, quatre (66%) sont décédés. Une recherche active et un suivi rapproché des patients VIH positifs présumés d'avoir une TBP indépendamment des résultats des investigations initiales pourrait réduire la morbidité et la mortalité dans ce groupe de patients vulnérables.

En el presente artículo se comunican los resultados de las investigaciones realizadas en 73 adultos ugandeses aquejados de infección por el virus de la inmunodeficiencia humana (VIH), en quienes existía la presunción clínica de tuberculosis pulmonar (TBP). Tras los exámenes iniciales se emitió el diagnóstico de TBP en 32 de los 73 pacientes. De los 41 pacientes restantes, clasificados inicialmente 'sin TBP', este diagnóstico se estableció de manera tardía en seis de ellos y la mediana del plazo hasta el diagnóstico fue 6 semanas. Se notificó la defunción de cuatro de los seis pacientes perdidos de vista durante el seguimiento (66%). La localización activa y el seguimiento estrecho de los pacientes con infección por el VIH y presunción clínica de TBP, sea cual fuere el resultado de las investigaciones iniciales, disminuirían la morbilidad y mortalidad en este grupo de pacientes vulnerables.