Surgical treatment of drug-resistant tuberculosis

Kempker, Russell R.; Vashakidze, Sergo; Solomonia, N; Dzidzikashvili, Nino; Blumberg, Henry M.

doi:10.1016/s1473-3099(11)70244-4

Cited by 94 publications

(78 citation statements)

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“…There is only one published case report evaluating SLD concentrations inside human cavitary lesions (9). Reports of worse clinical outcomes among patients with cavitary disease offer compelling but indirect evidence for low intracavitary SLD concentrations (10)(11)(12).…”

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confidence: 99%

Cavitary Penetration of Levofloxacin among Patients with Multidrug-Resistant Tuberculosis

Kempker

Barth

Vashakidze

et al. 2015

Antimicrob Agents Chemother

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A better understanding of second-line drug (SLD) pharmacokinetics, including cavitary penetration, may help optimize SLD dosing. Patients with pulmonary multidrug-resistant tuberculosis (MDR-TB) undergoing adjunctive surgery were enrolled in Tbilisi, Georgia. Serum was obtained at 0, 1, 4, and 8 h and at the time of cavitary removal to measure levofloxacin concentrations. After surgery, microdialysis was performed using the ex vivo cavity, and levofloxacin concentrations in the collected dialysate fluid were measured. Noncompartmental analysis was performed, and a cavitary-to-serum levofloxacin concentration ratio was calculated. Twelve patients received levofloxacin for a median of 373 days before surgery (median dose, 11.8 mg/kg). The median levofloxacin concentration in serum (C max ) was 6.5 g/ml, and it was <2 g/ml in 3 (25%) patients. Among 11 patients with complete data, the median cavitary concentration of levofloxacin was 4.36 g/ml (range, 0.46 to 8.82). The median cavitary/ serum levofloxacin ratio was 1.33 (range, 0.63 to 2.36), and 7 patients (64%) had a ratio of >1. There was a significant correlation between serum and cavitary concentrations (r ‫؍‬ 0.71; P ‫؍‬ 0.01). Levofloxacin had excellent penetration into chronic cavitary TB lesions, and there was a good correlation between serum and cavitary concentrations. Optimizing serum concentrations will help ensure optimal cavitary concentrations of levofloxacin, which may enhance treatment outcomes.T he emergence of multidrug-resistant tuberculosis (MDR-TB) remains a major barrier to global TB control (1). The treatment course for MDR-TB (with resistance to isoniazid and rifampin) consists of 18 to 24 months of second-line antituberculosis drugs (SLDs), including a fluoroquinolone and an injectable agent (amikacin, kanamycin, or capreomycin). A 2009 meta-analysis of MDR-TB treatment outcomes found an overall success rate of 62% with a range of 36 to 79% (2). The most recent World Health Organization (WHO) global TB report reported an overall successful outcome rate of 48%, again with a wide range (3). These data show that we are far from the goal of a Ͼ75% successful outcome treatment rate among MDR-TB patients; however, the broad range of successful outcomes suggests that we may be able to more effectively maximize existing SLD regimens. A better knowledge of how to optimize available SLD regimens could improve outcomes and provide important principles for the efficacious use of new drugs.The clinical pharmacology of SLDs has been a neglected area of research (4). Pharmacokinetic studies among patients with drugsusceptible TB demonstrate that low concentrations of first-line drugs are associated with poor clinical outcomes, and simulation studies have found that even with perfect adherence up to 1% of patients would develop further drug resistance during treatment due to variability in drug concentrations (5-7). A recent report on 25 patients with MDR-TB found that plasma SLD concentrations were frequently low and were associated with decreased drug ...

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confidence: 99%

Cavitary Penetration of Levofloxacin among Patients with Multidrug-Resistant Tuberculosis

Kempker

Barth

Vashakidze

et al. 2015

Antimicrob Agents Chemother

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“…In reported series, selection bias by indication is a potential flaw as patients who underwent surgery were perhaps younger or in a better clinical condition. However, even with these limitations, surgical resection has been suggested early in the course of treatment of MDR-TB [8,9]. A recent meta-analysis showed that the treatment effect of surgery added to chemotherapy was more pronounced in studies with extensively drug-resistant TB.…”

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Drug concentration in lung tissue in multidrug-resistant tuberculosis

et al. 2013

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Multidrug-resistant tuberculosis (MDR-TB) is emerging worldwide, with 3.7% of new cases and 20% of previously treated tuberculosis (TB) cases having MDR-TB. Unfortunately, second-line TB drugs, used for MDR-TB treatment, are less effective than first-line drugs [1]. Sputum culture rather than sputum smear microscopy is recommended to monitor treatment response [1]. Therapeutic drug monitoring (TDM), which may help optimise efficacy and minimise side-effects with the potential to safeguard intestinal absorption of drugs [2], is currently not recommended in World Health Organization (WHO) treatment guidelines [1]. Although TDM yields information on serum drug concentrations, penetration of second-line TB drugs into diseased tissues such as destroyed lung tissue has, to our knowledge, not been addressed in studies [3].Herein, we report simultaneous blood and tissue concentrations of second-line TB drugs in lung tissue destroyed by MDR-TB.

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“…Its place has recently been revised. [66][67][68] In patients with a new episode of MDR-TB, unilateral lung involvement and good general condition, surgery seems to improve the outcome whereas in patients in retreatment, with XDR-TB, bilateral disease or low body mass index, the outcome is poor.…”

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Tuberculosis Multidrug-resistant Tuberculosis – From Epidemiology to Treatment Design

Zellweger¹

2015

European Respiratory &Amp; Pulmonary Diseases

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Multidrug-resistant tuberculosis (MDR-TB) and extensively resistant tuberculosis (XDR-TB) are present in most regions of the world and represent a serious threat to the control of tuberculosis. They usually result from errors somewhere along the chain of management of the disease that favoured the selection of resistant mutants, progressively replacing drug-sensitive strains and transmitted to further patients. The currently recommended strategies for the control of this serious situation is the rapid identification of drug-resistant strains, careful drug management of patients with second-line drugs and prevention of the transmission of mycobacteria to contacts. Optimal selection and number of drugs and duration of treatment are not clearly defined. Prevention of the creation of additional cases of MDR-TB is crucial. KeywordsTuberculosis, multidrug-resistant tuberculosis (MDR-TB), extensively resistant tuberculosis (XDR-TB), treatment Disclosure: Jean-Pierre Zellweger has no conflicts of interest to declare. No funding was received for the publication of this article.Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit. The latest reports from the World Health Organization (WHO) estimate the number of MDR-TB to half a million cases, of which 10 % are XDR-TB, a large part being left untreated, with a high death burden.2 In some regions of the world or in some at-risk populations, like gold miners in South Africa, the rate of MDR-TB is increasing rapidly, particularly in previously treated cases, in spite of the fact that the global incidence rate in the same population had decreased during the same time period.3 Recent reports reveal alarming levels of drug-resistant TB in many Eastern European regions, 4 such as Belarus, where the rates reach 35.3 % in new patients and 76.5 % among previously treated cases 5 or in Ukraine, where the association with HIV seems to increase the problem. 6 In Russia, if the current trends continue, the incidence of drug-resistant TB could be higher than the incidence of drug-sensitive TB within the next few years.7 Prisons seem to be places where the incidence of TB (including drug-resistant forms) is particularly high. 7,8 In China, a recent survey concluded that the proportion of MDR-TB cases among new and previously treated patients is 5.7 % and 25.6 %, respectively, and the total number of MDR-TB cases is about 110,000. 9 The increase in drugresistant TB is also observed in children in some regions of the world.

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Surgical treatment of drug-resistant tuberculosis

Cited by 94 publications

References 50 publications

Cavitary Penetration of Levofloxacin among Patients with Multidrug-Resistant Tuberculosis

Cavitary Penetration of Levofloxacin among Patients with Multidrug-Resistant Tuberculosis

Drug concentration in lung tissue in multidrug-resistant tuberculosis

Tuberculosis Multidrug-resistant Tuberculosis – From Epidemiology to Treatment Design

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