Tb drug resistance pdf

Improving quality of patient data for treatment of. This reflects drug resistance acquired during tb treatment but may also reflect infection or re infection with resistant tb. Drug resistant tb can occur when the drugs used to treat tb are misused or mismanaged. Mycobacterium tuberculosis strains that are resistant to an increasing number of secondline drugs used to treat multidrug resistant tuberculosis mdr tb are becoming a threat to public health worldwide. Antimicrobial resistance invariably follows the introduction of new drugs.

Patients may have different concurrent conditions, such as hiv infection or diabetes. Summaries of unpublished data used for the recommendations 1. Drugresistance mechanisms and tuberculosis drugs ncbi. Amikacin and kanamycin are mainly used for treating multi drug resistant tuberculosis mdr tb in developing countries where there is a high rate of mdr tb. Multidrugresistant tuberculosis mdr tb resistance to at least isoniazid and rifampicin will influence the future of global tb control. Resistance to anti tb drugs is an escalating global health crisis. It emerges as a result of spontaneous gene mutations in m. Mdr tb, multidrugresistant tb, is defined by resistance to the two most commonly used drugs in the current four drug or firstline regimen, isoniazid and rifampin. Resistance to antitb drugs can occur when these drugs are misused or mismanaged. The vision of the end tb strategy of the world health organization who is for a world free of tuberculosis tb by the year 2035. Pdf tuberculosis epidemiology, pathogenesis, drugs and. The canadian tuberculosis laboratory surveillance system ctblss was created in 1998 to monitor emerging trends and patterns in tb drug resistance in canada. Who consolidated guidelines on drugresistant tuberculosis treatment 6 key definitions2 drug susceptibility testing dst refers to invitro testing using either phenotypic methods to determine susceptibility or molecular techniques to detect resistance conferring mutations to.

Drug resistance in malaria and in tuberculosis tb are major global health problems. Bedaquiline, pretomanid and linezolid for treatment of. Testing for drug resistance mutations curry international tb center webinar january 21, 2015 pennan barry, md, mph california mdr tb service surveillance and epidemiology section learning objective determine who should have rapid molecular testing for mutations associated with drug resistance to optimize early. An overview of drugresistant tb, including its causes, different types, treatment, economic toll, and more. Tuberculosis tb is nearly always curable if patients are treated with effective, uninterrupted antituberculous therapy. Xdr tb is a form of tb which is resistant to at least four of the core anti tb drugs. It is the result of interrupted, erratic, or inadequate tb therapy, and its spread is undermining efforts to control the global tb. The world health organization collects country data annually to monitor the response to mdr tb. Mar 23, 2017 molecular epidemiology tools have enabled researchers to show that primary resistancethe transmission of drugresistant tb from one person to anotheris playing a much larger role in the spread of drugresistant tb than previously thought. Worldwide emergence of extensively drugresistant tuberculosis. Who treatment guidelines for drug resistant tuberculosis, 2016 update. Drug resistance is a major challenge for tuberculosis tb treatment and eradication. A policy framework on decentralised and deinstitutionalised management for south africa will continue to guide provinces in the complex process of decentralisation of drug resistant tb care and treatment. This field guide for the management of drug resistant tuberculosis is a practical tool intended to help health workers in the clinical and operational management of the disease with special focus on the introduction, implementation and management of the 9month treatment regimen for multidrugresistant tuberculosis.

Xdr tb occurs when a mycobacterium tuberculosis strain is resistant to isoniazid and rifampin, two of the most powerful firstline drugs, as well as key drugs of the second line regimenany fluoroquinolone and at least one of the three injectable drugs shown above. Pdf pdf icon 275 kb report of expert consultations on rapid molecular testing to. Tb drug resistance is characterized by both the types of drugs to which the bacteria lack susceptibility and the manner in which resistance was acquired. Treatment of highly drugresistant pulmonary tuberculosis nejm. The treatment of multidrug and rifampin resistant tuberculosis mdrrr tb is complex. Mdrtb and resistance to any fluoroquinolone plus one secondline injectable drug was in fact the only combination of drug resistance significantly associated with an increased risk of death or failure unadjusted and adjusted ors were 2. Drug susceptible tb is the opposite of drug resistant tb.

Drug resistant tb globally in 2018, 484 000 417 000556 000 people developed tb that was resistant to o rifampicin resistant rr tb, the most effective firstline drug, and of. Pdf pdf icon 275 kb report of expert consultations on rapid molecular testing to detect drug resistant tuberculosis in the united states. Tuberculosis drug resistance and hiv infection, the netherlands. Provided by the centers for disease control and prevention cdc. Take a recent study on drugresistant tb in south africa in the new england journal of medicine. Introduction this fifth edition of the guidelines for surveillance of drug resistance in tuberculosis is an updated version of earlier editions published in 1994 1, 1997 2, 2003 3 and 2009 4. In certain areas, however, control programs have been inadequate because of low levels of treatment,inadequate drug supply,poor compliance or combinations of these factors,19,20. Resistance to isoniazid inh was observed in 1 of 2 patients 0. Pdf drug resistance in mycobacterium tuberculosis researchgate. From a cost perspective, drug resistance consumes a. Experts involved in the development of the who treatment guidelines for. Best practices in engagement of all health care providers in the management of drug resistant tuberculosis. Although the terms multidrug resistant tb and extensively drug resistant tb are precisely defined, the term multidrug resistance is often loosely used when discussing malaria.

Laird method mdrtb among previously treated tb patients acquired drug resistance is defined as resistance to isoniazid and rifampin drugs in patients that have been treated for tb. In an mdr tb cohort from the country of georgia, drug susceptibility testing for secondline drugs slds was performed at baseline and every third month. Fda approves new treatment for highly drugresistant forms. It involves resistance to the two most powerful anti tb drugs, isoniazid and rifampicin, also known as multidrug resistance mdr tb, in addition to resistance to any of the fluoroquinolones such as ofloxacin or moxifloxacin and to at least one of three injectable secondline drugs amikacin, capreomycin or. Globally, only half of multidrug resistant tuberculosis mdrtb. Tuberculosis management refers to the medical treatment of the infectious disease tuberculosis tb the standard short course treatment for tb is isoniazid along with pyridoxal phosphate to obviate peripheral neuropathy caused by isoniazid, rifampicin also known as rifampin in the united states, pyrazinamide, and ethambutol for two months, then isoniazid and rifampicin. Detroit tb program wayne state university school of medicine tristate tb intensive workshop columbus, ohio september 26, 2018 disclosures financial none 10 medications are approved by the fda for tb inh, rif, rifapentine, pza, emb, streptomycin, cycloserine. In recent years, even more serious forms of drug resistance have been reported. Multidrugresistant tuberculosis mdrtb oxford academic. Although russia is dauntingly expecting an upsurge in the numbers of cases of mdr tuberculosis and rifampicinresistant tuberculosis 27% in new and 63% in previously treated cases, it has not released data from its national antituberculosis survey yet. Some forms of tb are also resistant to secondline medications, and are called extensively drug resistant tb. Who treatment guidelines for drug resistant tuberculosis. Drug resistant tuberculosis tb has emerged as a significant global epidemic and poses a serious threat to hivinfected persons.

Tuberculosis tb is a serious public health problem worldwide. Reports of extensively drug resistant xdr tb, defined as mdr tb. Pdf drug resistance mechanisms in mycobacterium tuberculosis. Nov 15, 2019 the document includes recommendations on the treatment of multidrugresistant tb mdr tb as well as isoniazidresistant but rifampinsusceptible tb. Tb is caused by mycobacterium tuberculosis, bacteria that usually attack the lungs. The emergence of drug resistant tuberculosis tb, particularly multidrugresistant mdr and extensively drug resistant xdr tb, is a major public health problem. Drugresistant tuberculosis curry international tuberculosis center. A better knowledge of the mechanisms of action of anti tb drugs and the development of drug resistance will allow identifying new drug targets and better ways to detect drug resistance. Guidelines for surveillance of drug resistance in tuberculosis 5th edition file size. Drug resistance mechanisms in mycobacterium tuberculosis. Pdf pdf icon 349 kb plan to combat extensively drug resistant tuberculosis mmwr 2009. Extensively drugresistant tb xdr tb extensively drugresistant tb xdr tb is a rare type of mdr tb that is resistant to isoniazid and rifampin, plus any fluoroquinolone and at least one of three injectable secondline drugs i. The latest anti tb drug resistance surveillance data show that 3.

When to use rapid molecular tests for drug resistance. Drug resistant tb multidrug resistant tb mdr tbresistant to at least rifampin rif and isoniazid inh 3. Its situation is worsened by the presence of multidrug resistant mdr strains of mycobacterium tuberculosis, the. Treatment requires a combination of multiple agents and often needs to be individualized, taking numerous considerations into account 1,2. A potential threat to this is the lack of effective treatment for intolerant or nonresponsive multi drug resistant tb mdr tb, with resistance to isoniazid and rifampicin or extensively drug resistant tb xdr tb, mdr tb with additional resistance. Some studies found strongly increased risks for multidrugresistant tb mdr tb among patients coinfected with tb and hiv 37, whereas other studies found no increased risk 811. The burgeoning epidemic of drug resistant dr tb threatens to destabilise tb control in highburden settings, particularly in africa. In this study in south africa, a new agent, pretomanid, was. Reports on associations of hiv coinfection and drug resistance among patients with tb have been contradictory. A policy framework on decentralised and deinstitutionalised management for south africa will guide provinces in the complex process of decentralisation of drug resistant tb care and treatment. The main resistance mechanism to the anti tuberculosis drug is the mutation of the target gene accountable for the action of anti tuberculosis drugs.

Epidemiology of multidrugresistant tuberculosis mdrtb in. Prevalence and detection of drug resistant mutations in. National center for hivaids, viral hepatitis, std, and tb prevention. If someone is infected with tb bacteria that are fully susceptible, it means that all of the tb drugs will be effective so long as they are taken properly. New york august 14, 2019pretomanid, a novel compound developed by the nonprofit organization tb alliance, was approved by the u. No resistance to fluoroquinolones fq or kanamycin kan was observed. Review an update on pathogenesis and management of tuberculosis with special reference to drug resistance article pdf available in asian pacific journal of tropical disease 59. Community transmission secondary resistance acquired resistance develops during tb therapy. It is the result of interrupted, erratic, or inadequate tb therapy, and its spread is undermining efforts to control the global tb epidemic. Who treatment guidelines for drugresistant tuberculosis, 2016 update. Evolution of drug resistance in mycobacterium tuberculosis. Report warns of rise in drugresistant tuberculosis cidrap. Resistance to single agents is the most common type. Drug resistant strains of tuberculosis tb pose a serious threat to tb prevention and control efforts.

In this study in south africa, a new agent, pretomanid, was combined with bedaquiline and linezo. Overall, the prevalence of the resistance to first and secondline tb drugs was 1. Resistance to antitb drugs is an escalating global health crisis. The number of drug resistant tb dr tb cases is increasing worldwide. Multi drug resistant tuberculosis mdr tb is a form of tuberculosis tb infection caused by bacteria that are resistant to treatment with at least two of the most powerful firstline anti tb medications drugs, isoniazid and rifampin. Adherence to treatment is critical for cure of individual patients, controlling spread of infection, and minimizing the development of drug resistance. A situation assessment tool to engage all relevant care providers in drug resistant tuberculosis dr tb management at country level. Pdf tuberculosis tb is a serious public health problem worldwide. The document takes into account recent advancements in laboratory. Recent declines in the clinical effectiveness of antimalarial drugs, including artemisininbased combination therapy, have. In 2017, an estimated 558 000 new cases of mdrrr tb. Several fact sheets on drug resistant tb, including symptoms, risks, treatment, and more. Coverage of rpob 5 0 8 5 0 9 5 1 0 5 1 1 5 1 2 5 1 3 5. Drugresistant tb transmitted same way as drugsusceptible tb drug resistance is divided into two types primary resistance develops in persons initially infected with resistant organisms.

Apr 12, 20 in 2009, we proposed the term totally drugresistant tuberculosis tdrtb for tb strains that showed invitro resistance to all first and second line drugs tested isoniazid, rifampicin, streptomycin, ethambutol, pyrazinamide, ethionamide, paraaminosalicylic acid, cycloserine, ofloxacin, amikacin, ciprofloxacin, capreomycin, kanamycin. Citc is a project of the university of california, san francisco, funded by the centers for. Bedaquiline and delamanid, novel classes of anti tuberculosis drugs, have been recently approved for the treatment of multidrug resistant tuberculosis. Prevalence of drugresistant tuberculosis in south africa. This field guide for the management of drugresistant tuberculosis is a practical tool intended to help health workers in the clinical and operational management of the disease with special focus on the introduction, implementation and management of the 9month treatment regimen for multidrug resistant tuberculosis. In 2006, there were an estimated 489,000 new cases of multidrug resistant mdr tb which is tb that is resistant to at least isoniazid and rifampinand 116,000 estimated deaths. Jul 02, 2014 drug resistance in tb remains a manmade phenomenon.

Tb experts should be consulted in the treatment of mdr tb. A survival guide for clinicians, third edition was created through a collaboration of the curry international tuberculosis center citc and the state of california department of public health, tuberculosis control branch cdph. Extensive drug resistance in malaria and tuberculosis. Acquired drug resistance in mycobacterium tuberculosis and. Treatment of drug resistant tb treatment options for highly drug resistant tuberculosis are limited. Treatment of highly drugresistant pulmonary tuberculosis. Its situation is worsened by the presence of multidrug resistant mdr strains of mycobacterium tuberculosis, the causative agent of the disease.

Tuberculosis tb is a serious disease caused by bacteria that are spread from person to person through the air. We surveyed the network of supranational reference laboratories for m. Among the reasons for this, the noncompliance with the treatment regimens is signaled as the first cause. Multi drug resistant mdr tb strains show resistance to rifampicin and. These actions will contribute to the prevention of further resistance to tb drugs and significantly reduce the global spread of mdr tb. A recent cdc study found that direct costs for treatment including drugs, diagnostics, case management, hospitalization, etc. It still means that several drugs need to be taken together to provide effective tb treatment.

Guidelines for surveillance of drug resistance in tuberculosis. Types of resistance tb treatment requires four firstline antibiotics. The financial toll of drug resistance treatment for drug resistant tb is very expensive. A worldwide yearly survey of new data in adverse drug reactions. Multi drug and extensively drug resistant tb represents the major barrier in the prevention and control of the disease. Mdr tb, multidrug resistant tb, is defined by resistance to the two most commonly used drugs in the current four drug or firstline regimen, isoniazid and rifampin. Rates and risk factors for acquired drug resistance and association with outcomes among patients with multidrugresistant tuberculosis mdr tb are not well defined. Who consolidated guidelines on drugresistant tuberculosis. Xdr tb strains may also be resistant to additional drugs, greatly complicating. Who guidelines for surveillance of drug resistance in. We hope it will receive due consideration and support among. This fifth edition of the guidelines for surveillance of drug resistance in tuberculosis is an updated version of earlier editions published in 1994 1, 1997 2, 2003 3 and 2009 4.

Effective treatment for tb has been available for over 30 years in many countries. It involves resistance to the two most powerful anti tb drugs, isoniazid and rifampicin, also known as multidrug resistance mdr tb, in addition to resistance to any of the fluoroquinolones such as ofloxacin or moxifloxacin and to at least one of three injectable secondline drugs amikacin. Drug resistant tb develops when the antibiotics used to treat tb are misused or mismanaged, and it can spread. The global burden of tb remains alarmingly high, with. Its situation is worsened by the presence of multidrug resistant mdr strains of.