5 курс / Пульмонология и фтизиатрия / Clinical_Tuberculosis_Friedman_Lloyd_N_,_Dedicoat

Introduction

Guidelines for reading the tables

Drug-sensitive tuberculosis

References

INTRODUCTION

This chapter is designed to compare and give guidance on options for treatment recommended by established national and international organizations. Generally, practitioners should follow the guidelines specified by the organization that represents the geographical location of the treatment facility. These recommendations are a guide and should not be substituted for the detailed information in the guidelines themselves and should not be substituted for the opinion of an expert consultant. Although many of these regimens can be applied to the treatment of extrapulmonary disease, it would be prudent to refer to the chapter on Extrapulmonary Tuberculosis for guidance, as well as, where indicated, the chapters on Pulmonary Tuberculosis, Tuberculosis and Human Immunodeficiency Virus Co-infection, Tuberculosis in Childhood and Pregnancy, and Drug Resistant Tuberculosis.

●●ATS: American Thoracic Society

●●CDC: Centers for Disease Control and Prevention

●●CTS: Canadian Thoracic Society

●●Curry: Curry International Tuberculosis Center

●●ERS: European Respiratory Society

●●IDSA: Infectious Disease Society of America

●●IUATLD: International Union Against Tuberculosis and Lung Disease

●●NICE: National Institute for Health and Care Excellence

●●NTCA: National Tuberculosis Controllers Association

●●WHO: World Health Organization

Drug Abbreviations: Am = amikacin; Bdq = bedaquiline; Cfz = clofazimine; Clv = clavulanic acid; Cs = cycloserine; Dlm = delaminid; E = ethambutol; Fq = fluoroquinolone (Lfx or Mfx); H = isoniazid; HH = high-dose isoniazid; Ipm-Cln = imi- penem-cilastatin; Km = kanamycin; Lfx = levofloxacin;

393

393

393

398

Lzd = linezolid; Mfx = moxifloxacin; Mpm = meropenem; P = rifapentine; PAS = para-aminosalicylic acid; Pto/Eto = prothionamide/ethionamide; R = rifampin; S = streptomycin; Trd = terizidone; Z = pyrazinamide

GUIDELINES FOR READING

THE TABLES

The first number reflects the number of months to administer the drugs.

Numbers within parentheses reflect number of times per week; if no parentheses are present, daily therapy is indicated.

Within each column, the first row represents the initiation phase, and the second row is the continuation phase. For example, 2HRZE represents 2 months of initial therapy with isoniazid, rifampin, pyrazinamide and ethambutol, and on the line following, 4HR represents 4 months of maintenance therapy with isoniazid and rifampin. Similarly, 2HRZE (3) represents 2 months of isoniazid, rifampin, pyrazinamide, and ethambutol given thrice weekly. Usually, the drug dosages for intermittent therapy are higher than for daily therapy.

DRUG-SENSITIVE TUBERCULOSIS

The usual therapy for drug-sensitive tuberculosis (TB) comprises four drugs for 2 months, dropping ethambutol once the organism is known to be sensitive to isoniazid, rifampin, and pyrazinamide; then continuing maintenance isoniazid and rifampin for 4 months. In the United States,1 if the person has cavitary disease and is culture positive 2 months after starting treatment, maintenance therapy is extended to 7 months for

a total of 9 months of therapy (see Table 20.1). Consideration also can be given to extending therapy for cavitary disease or a positive 2-month culture based on clinical expertise, such as extensive disease or the existence of medical comorbidities that might cause a delay in response. HIV-positive individuals who are not on antiretroviral therapy should have maintenance therapy extended to 7 months. Decisions on when to start antiretroviral therapy, as well as drug interactions, in persons with TB who are newly diagnosed with HIV may be found in the chapter on Tuberculosis and Human Immunodeficiency Virus Co-infection.

Individuals should receive therapy weekdays by directly observed therapy (DOT), be evaluated monthly by the clinician, and obtain a sputum for acid-fast bacilli (AFB) each month until 2 consecutive monthly sputum examinations are negative. Ethambutol should be discontinued once the organism is known to be pansensitive. HIV-positive persons and persons with cavitary disease should take a daily regimen. It is considered acceptable to give only five doses per week by DOT, even if the individual

Table 20.2  Isoniazid monoresistant TB treatment regimens1,3–5,9

does not take the weekend doses. If an individual is intolerant to one of the drugs and it must be discontinued, the individual should be treated as if resistant to that drug (e.g., if isoniazid is stopped because of hepatitis, then an isoniazid monoresistant regimen should be used).1,9

Isoniazid monoresistant TB

In most cases, isoniazid monoresistant TB can be cured with a 6-month regimen without using injectable drugs. (Table 20.2).1,3–9

Multidrug-resistant TB

Multidrug-resistant tuberculosis (MDR-TB) can be treated, according to the WHO, without injectable agents in a regimen that usually lasts for at least 18 months. The prioritization of medications is noted in Table 20.3.7 It is essential that the person be taking at least four medications to which the organism is sensitive for the first 24 weeks, at which time bedaquiline is discontinued

Group B (add at least one if all of the Group A medications are not used

Group C (add to complete a regimen of at least four, preferably five, drugs when medicines from Groups A or B cannot be used)

Clofazimine

Cycloserine or terizidone

Ethambutol

Delamanida Pyrazinamide (if sensitive)

Imipenem-cilastatinb or meropenemb

Amikacin or streptomycin (only if sensitive, and hearing tests available) Ethionamide or prothionamide

Para-aminosalicylic acid

leaving three effective drugs for the remainder of treatment. Ideally, fluoroquinolone testing at a minimum should be performed before starting treatment. It is preferred that all three drugs from group A and at least one drug from group B be used. WHO suggests starting five drugs in case one drug has to be discontinued due to side effects.7 The person should be culture negative (i.e., three consecutive negative monthly cultures) for at least 15 months from the time of the first negative culture of the series. If amikacin is started, it is recommended for at least 6 months. Streptomycin is an acceptable alternative. Kanamycin and capreomycin are not considered acceptable drugs due to high rates of failure. There is no definite cutoff, in terms of months treated, to define treatment failure; data show that the percentage of treatment failure if culture positive at 5, 6, 7, and 8 months is 10.3%, 16.4%, 24.7%, and 44.5%, respectively.7 The ATS/CDC/ERS/IDSA guidelines9 also recommend an all-oral regimen starting with five drugs (see Table 20.4).

Rifampin monoresistant TB

The WHO regimen for rifampin monoresistance is exactly the same as the MDR-TB regimen.7 The new ATS/CDC/ERS/IDSA guidelines do not address rifampin monoresistance; the recommendations from the Curry International Tuberculosis Center do address it (Table 20.5).11 One can be less aggressive with rifampin monoresistance in some developed countries because, where better resources are available, one can be more confident that rifampin is the only resistant drug. Before the inclusion of rifampin in TB regimens in 1980, isoniazid and ethambutol for 18 months was the standard regimen and was used with great success. Although there are no direct studies, it is felt that this regimen can be shortened to 12 months if a fluoroquinolone such as levofloxacin is added and pyrazinamide is used for the first 2 months. Although an injectable has been suggested to shorten the regimen, the goal is to avoid injectable agents wherever possible.

MDR-TB treatment regimens

Table 20.4 shows multiple long daily regimens (12–21 months) and one short daily regimen (at least 9 months) for MDR-TB. The long regimens are standard. The short intensive WHO regimen includes additional drugs plus an injectable agent, although a recent WHO communication allows for substitution of bedaquiline for the injectable agent.10 In persons with MDR-TB who were not previously treated with second-line drugs, do not have central nervous system or disseminated TB, and in whom resistance to fluoroquinolones and second-line injectable agents (or bedaquiline if substituted) was excluded or is considered highly unlikely, the short intensive MDR-TB regimen may be used instead of the long regimen; these individuals must not previously have received any TB treatment for 1 month or more. Amikacin may be substituted for kanamycin, although now it is recommended that bedaquiline be substituted for the injectable agent so that it is an all-oral regimen.3–5,7–10

Extensively drug-resistant tuberculosis

Extensively drug-resistant tuberculosis (XDR-TB) is defined as resistance to isoniazid and rifampin, a fluoroquinolone, and one of the following three injectable agents: amikacin, kanamycin, or capreomycin.9

For pre-XDR and XDR-TB, one can use the same approach as the ATS/CDC/ERS/IDSA recommendations for MDR-TB treatment in terms of number of susceptible drugs, initially five if possible, but with a longer duration of treatment (15–24 months after culture conversion).9 The WHO recommendations also can be adapted. Expert consultation is necessary.

New XDR-TB regimen

Pretomanid was approved by the United States Food and Drug Administration as part of a three-drug regimen to treat highly resistant TB (predominantly XDR-TB but also MDR-TB that is

WHO

Long course (at least 18 months total): Start with at least four drugs (preferably five) to which the organism is sensitive:

All three from Group A plus at least one, preferably two, from Group B plus drugs from Group C if at least four drugs cannot be chosen from Groups A and B. At 24 weeks, Bdq is discontinued and the remaining three to four drugs are used for 15 months after culture conversion.

Short course: 9 months (The length of initial therapy can be extended depending on sputum smear conversion)

4MfxKmEtoCfzHHZE

5MfxCfzZE

WHO recently (December 2019) recommended substituting 6 months of Bdq for the injectable agent.10 Lfx may be substituted for Mfx.

a Can substitute a different injectable. The latest literature suggests amikacin.9

nonresponsive or treatment intolerant). The regimen comprises bedaquiline, pretomanid, and linezolid for 6 months with an option to extend for a longer duration and is an all-oral regimen. Six months after completion of treatment, the regimen showed an efficacy of 90% which was defined as two consecutive negative cultures and no relapse in the subsequent 6 months. This is much better than the average historical control regimen efficacy of 14% for the treatment of XDR-TB.12

Latent tuberculosis infection

For many years, the standard for the treatment of presumably pansensitive latent tuberculosis infection (LTBI) was either 9 or 6 months of isoniazid. More recently, shorter regimens have been shown to be equivalent and are fast gaining popularity because of increased adherence, safety, and economy of resources (Table 20.6).4–6,13,14

Some of the nuances of treatment of LTBI are discussed in the bullets below:

●●Nine months of isoniazid versus 6 months of isoniazid:

9 months is clearly a more effective regimen. The very study that is cited to justify the usefulness of a 6-month regimen is the same study that showed that it is less effective.15 The study compared 12 months versus 6 months of isoniazid. Although nearly comparable for all participants who took a 12 versus

a 6 month regimen, when analyzed only for those who were adherent, a 12-month regimen was 93% effective versus a 6-month regimen which was 69% effective. The 12-month regimen was clearly superior, but was subsequently shortened to 9 months when it was shown that most of the benefit of a 12-month regimen had already occurred by 9–10 months of therapy.16

●●The WHO recommends 36 months of isoniazid ­preventive therapy for individuals who are HIV-positive who reside in high TB incidence countries13 (see also the chapter on Tuberculosis and Human Immunodeficiency Virus

Co-infection for information about this and other regimens, as well as drug interactions with antiretroviral therapy).

●●WHO now recommends one month of isoniazid and rifapentine for HIV-positive and HIV-negative individuals with LTBI.13 The IUATLD recommends this treatment only for HIV-positive individuals.6

●●If a person with LTBI is a contact to a person with TB who is resistant to either isoniazid or rifampin, that drug should not be used.

●●For a person with LTBI who was a known contact to someone with MDR-TB, a fluoroquinolone for 6–12 months with or without a second drug, based on source isolate sensitivities, can be used. Pyrazinamide generally should be avoided.9

Circumstances where it is not clear whether the patient has active or inactive TB

It often is found that an individual has a fibrotic lesion or density in an upper lobe and a positive test for LTBI. If it is not clear whether the radiographic abnormality represents active or inactive disease, and there is reasonable concern that it is active, a chest radiograph or chest CT can be used as a baseline evaluation, a sputum culture for acid fast bacilli should be obtained, and the person can be started on HRZE. If, after 2 months, the culture is negative and the chest radiograph or CT is unchanged, then the disease most likely is inactive; the person has received adequate treatment for LTBI and the drugs can be stopped. This is because rifampin and pyrazinamide for 2 months was proved to be an effective regimen to treat LTBI, but is no longer recommended, as noted earlier. If the culture is negative and the chest radiograph or CT improves, the person can be considered to have culture-negative TB and treatment with isoniazid and rifampin

can continue for another 2 months for a total of 4 months of therapy. If the culture is positive, the person is treated for the usual 6 months.1 If it is very unlikely that the lesion is active, cultures can be obtained and, if negative, a standard LTBI regimen can be administered.

REFERENCES

\1.\ Nahid P et al. ATS/CDC/IDSA clinical practice guidelines: Treatment of drug-susceptible tuberculosis. Clin Infect Dis. 2016;63:e147–95.

\2.\ Guidelines for Treatment of Drug-Susceptible Tuberculosis and Patient Care, 2017 update. Geneva: World Health Organization; 2017. Licence: CC BY-NC-SA 3.0 IGO.

\3.\ Migliori GB et al. European union standards for tuberculosis care. Eur Respir J. 2012;39:807–19, doi: 10.1183/09031936.00203811

\4.\ National Institute for Health and Care Institute. Tuberculosis: NICE Guideline. http://nice.org.uk/guidance/ng33

\5.\ Canadian Tuberculosis Standards: 7th edition, Available at: https:// strauss.ca/OEMAC/wp-content/uploads/2013/11/Canadian_TB_ Standards_7th-edition_English.pdf

\6.\ Dlodlo RA et al. Management of Tuberculosis: A Guide to Essential Practice. Paris, France: International Union Against Tuberculosis and Lung Disease, 2019.

\7.\ WHO Consolidated Guidelines on Drug-Resistant Tuberculosis Treatment. Geneva: World Health Organization, 20, 2019. Licence CC BY-NC-SA 3.0 IGO.

\8.\ Piubello A et al. Field Guide for the Management of DrugResistant Tuberculosis. Paris, France: International Union Against Tuberculosis and Lung Disease, 2018.

\9.\ Nahid P et al. Treatment of drug-resistant tuberculosis. An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline. Am J Respir Crit Care Med. 2019;200(10):e93–142.

\10.\ WHO. Rapid Communication: Key changes to the treatment of drug-resistant tuberculosis. December 2019. https://www.who.int/ tb/publications/2019/WHO_RapidCommunicationMDR_TB2019. pdf?ua=1

\11.\ Curry International Tuberculosis Center and California Department of Public Health. Drug-resistant tuberculosis: A survival guide for clinicians, 3rd ed., 2016.

\12.\ Conradie F et al. Treatment of highly drug-resistant pulmonary tuberculosis. NEJM. 2020;382:893–902.

\13.\ WHO Consolidated Guidelines on Tuberculosis: tuberculosis preventive treatment. Geneva: World Health Organization; 2020. Licence: CC BY-NC-SA 3.0 IGO.

\14.\ Sterling TR et al. Guidelines for the treatment of latent tuberculosis infection: Recommendations from the National Tuberculosis Controllers Association and CDC, 2020. MMWR Recomm Rep. 2020;69:1–11.

\15.\ IUATLD. Efficacy of various durations of isoniazid preventive therapy for tuberculosis: Five years of follow-up in the IUAT trial. International Union Against Tuberculosis Committee on Prophylaxis. Bull World Health Org 1982;60(4):555–64.

\16.\ Comstock GW. How much isoniazid is needed for prevention of tuberculosis among immunocompetent adults? Int J Tuberc Lung Dis. 1999;3:847–50.