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Capreomycin
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Capreomycin is an important reserve antibiotic for the treatment of tuberculosis and has been used for this purpose for more than 40 years (Cohen and Yue, 1966; Cuthbert and Bruce, 1964; Kass, 1965). It is a naturally produced cyclic polypeptide composed of nonproteinogenic amino acids and biosynthesized by a nonribosomal protein synthase by Streptomyces capreolus (Barkei et al., 2009; Chopra et al., 2012; Felnagle et al., 2008; Thomas et al., 2003). Capreomycin was first isolated in 1959 from S. capreolus at the Lilly Laboratories in Indiana (Herr et al., 1959). It consists of four microbiologically active compounds—capreomycin IA, IB, IIA, and IIB in the approximate proportions of 25%, 67%, 3%, and 6%, respectively (Chopra et al., 2012; Herr and Redstone, 1966; Nomoto et al., 1977; Shiba et al., 1976). For clinical purposes, capreomycin is given as a sulfate (predominantly capreomycin IA and IB). The chemical structures of capreomycin IA and IB are shown in Figure 134.1.
Nanomaterials in tuberculosis DNA vaccine delivery: historical perspective and current landscape
Published in Drug Delivery, 2022
Xing Luo, Xiaoqiang Zeng, Li Gong, Yan Ye, Cun Sun, Ting Chen, Zelong Zhang, Yikun Tao, Hao Zeng, Quanming Zou, Yun Yang, Jieping Li, Hongwu Sun
Tuberculosis (TB), causing 1.5 million deaths in 2020 (Ghebreyesus, 2022, Zaman, 2010), is a significant global threat to human health. In this year, an estimated 10 million people worldwide have been infected with TB (Ghebreyesus, 2022), with 1 million new patients (Ghebreyesus) reported in 2021 (according to the World Health Organization), and 842,000 (World Health Organization, 2020) new cases in China in 2020. On an average, 49% TB patients spend more than 20% (in the range of 19–83%) of their annual household income on TB treatment (Viney et al., 2021),which is a challenging process due to numerous reasons (Figure 1). It involves the circumvention of phagocytic fusion and its destruction (I), a neutralization of the acidic environment (II), an inhibition of envelope formation in apoptosis (III), the suppression of plasma-membrane repair and immune-cell activation (IV–V), and the restriction of pro-inflammatory responses (VI) (Sampath et al., 2021). Although a combination of first-line (isoniazid, rifampicin, ethambutol, and streptomycin) and second-line (amikacin, kanamycin, and capreomycin) drugs is useful for TB treatment, their utility is limited by the prevalence of multidrug-resistant TB (MDR-TB) (Marks et al., 2014), extensively drug-resistant TB (XDR-TB) (Mullerpattan et al., 2019), and HIV superinfection.
An expert opinion on respiratory delivery of high dose powders for lung infections
Published in Expert Opinion on Drug Delivery, 2022
Bishal Raj Adhikari, Jack Dummer, Keith C. Gordon, Shyamal C. Das
The application of high dose powder is an area of continued interest. Antibiotic resistance is an increasing problem worldwide, as recognised by the World Health Organisation (WHO) [131]. High dose dry powder delivery has been developed as a realistic strategy to deliver drugs, particularly for local action in lung infections. In the case of multidrug resistant tuberculosis (MDR-TB), the number of antimicrobials available to treat the tuberculosis pathogen has dropped [132,133]. In recent decades, this crisis has further escalated as only a limited number of new molecules have been approved. Since the 1960s, bedaquiline, delamanid, and pretomanid are the only novel drugs that were approved for the treatment of MDR-TB, while fluoroquinolones have been repurposed for TB treatment [134–137]. This small pool of antibiotics available for TB treatment has been further depleted since 2020, when the WHO recommended against the use of kanamycin and capreomycin for the treatment of MDR-TB due to their associated side-effects of ototoxicity and nephrotoxicity [133].
Safety implications of combined antiretroviral and anti-tuberculosis drugs
Published in Expert Opinion on Drug Safety, 2020
Maddalena Cerrone, Margherita Bracchi, Sean Wasserman, Anton Pozniak, Graeme Meintjes, Karen Cohen, Robert J Wilkinson
Shared toxicity is the major challenge with concomitant use of ART and anti-TB drugs [15,112]. It is unclear whether risk of adverse reactions to TB treatment are increased with concurrent ART administration [113], but identification of the culprit drug is often difficult and complicates management of both infections when toxicity occurs [15,114]. Hepatotoxicity, peripheral neuropathy, central nervous system side effects, QT prolongation, and cutaneous adverse drug reactions are the most important toxicities that can arise during co-administration of ART and anti-TB drugs and will be discussed in detail below. Other important adverse reactions include nephrotoxicity and electrolyte abnormalities with injectable agents (aminoglycosides and capreomycin) and tenofovir disoproxil fumarate [115]. Gastrointestinal (GI) disturbances, such as diarrhea, nausea, vomiting and abdominal pain are events associated with all antiretrovirals (ARV), especially the PI and in particular lopinavir/ritonavir. Notably, GI side effects are an important cause of interruption of lopinavir/ritonavir-based ART [116]. Among anti-TB drugs, ethionamide and para-aminosalicylic acid are most frequently associated with GI intolerance. Hypothyroidism can occur in over a half of patients treated for DR-TB, and is associated with exposure to para-aminosalicylic acid and ethionamide [117,118]. Ototoxicity is another important side effect of aminoglycosides (streptomycin, kanamycin, amikacin). Therefore, audiometry monitoring is recommended at baseline and during treatment with aminoglycosides [119]