Aura 2016: first Australian report on antimicrobial use and resistance in human health

4.5 Mycobacterium tuberculosis

Health impact

M. tuberculosis is the bacterium that causes tuberculosis, an infection that has a range of clinical manifestations, but most commonly presents as lung disease. Once acquired, M. tuberculosis can remain quiescent in the body for many years (even decades) as latent tuberculosis. When the body’s defences wane, it reactivates and causes active disease. Tuberculosis is a significant public health issue in many countries. Australia is fortunate in having one of the lowest rates of tuberculosis in the world; however, continued vigilance is required to maintain or improve on this low rate. About 85% of all notified cases in Australia are found in the overseas-born population, who have mostly migrated from high-prevalence countries.

Treatment

M. tuberculosis is not susceptible to most conventional antibacterial agents. Instead, it requires treatment with specially designed antimycobacterial agents. Four of these – isoniazid, rifampicin, ethambutol and pyrazinamide – are the first-line agents and comprise the standard oral treatment regimen for tuberculosis caused by fully susceptible strains. When the strain is susceptible, isoniazid is considered the mainstay of therapy. Combinations of antimycobacterial agents are always required for treatment because resistance to any of them can emerge during treatment. Treatment is required for a minimum of six months.

Types and impact of resistance

Because such a high proportion of Australian cases occur in people born overseas, changes in antimicrobial susceptibility observed in Australia reflect patterns of resistance in these other countries. The most common forms of resistance worldwide are resistance to isoniazid and rifampicin. When strains are resistant to one or both of these, additional antimycobacterial agents are added to, or substituted into, the treatment combination. For most of these additional agents, side effects are more likely or more severe. Longer courses of treatment are needed for resistant strains.

Strains that are resistant to isoniazid and rifampicin, with or without resistance to the other two first-line agents, are considered to be multidrug-resistant tuberculosis (MDR-TB). If these strains are also resistant to fluoroquinolones and at least one injectable agent (amikacin, capreomycin, kanamycin), they are considered to be extremely drug-resistant tuberculosis (XDR-TB). Treatment success is significantly lower, and costs are significantly higher, for MDR-TB, and even more so for XDR-TB.

Treatment success is significantly lower, and costs are significantly higher, for MDR-TB, and even more so for XDR-TB.

Key findings (national)

In 2014, 1339 cases of tuberculosis were notified nationally (5.7 cases per 100 000 population). Of these cases, 1027 had positive laboratory cultures and susceptibility test results available. Overall rates of resistance to the four first-line agents and selected additional agents are shown in Figure 4.16.

Figure 4.16 Mycobacterium tuberculosis resistance to individual first-line agents and selected additional agents, 2014

AMI = amikacin; CAP = capreomycin; EMB = ethambutol; FLQ = fluoroquinolones; INH = isoniazid; INN = ethionamide; KAN = kanamycin; PZA = pyrazinamide; RIF = rifampicin

Notes:

1. First-line agents (dark columns) reported against (almost) all strains: isoniazid, rifampicin, ethambutol and pyrazinamide; selected additional agents (light columns) tested against isolates with resistance to first-line agents or from patients with severe adverse reactions to first-line agents.

2. Fluoroquinolones tested were ciprofloxacin, ofloxacin, moxifloxacin or levofloxacin.

Source: National Notifiable Diseases Surveillance System (national)

Data table: Figure 4.16

Agent	Type of agent	% resistant
Isoniazid (n = 1004)	First line	8.5
Rifampicin (n = 1027)	First line	2.4
Ethambutol (n = 1014)	First line	1.2
Pyrazinamide (n = 971)	First line	2.1
Fluoroquinolones (n = 54)	Selected additional	9.3
Kanamycin (n = 44)	Selected additional	9.1
Capreomycin (n = 53)	Selected additional	1.9
Amikacin (n = 52)	Selected additional	1.9
Ethionamide (n = 53)	Selected additional	35.8

Jurisdictional rates

There was some variation in resistance rates to first-line agents across states and territories (Figure 4.17).

Figure 4.17 Mycobacterium tuberculosis resistance to first-line agents, by jurisdiction, 2014

ACT = Australian Capital Territory; NSW = New South Wales; NT = Northern Territory; Qld = Queensland; SA = South Australia; Tas = Tasmania; Vic = Victoria; WA = Western Australia

Source: National Notifiable Diseases Surveillance System (national)

Data table: Figure 4.17

Jurisdiction	Isoniazid (% resistant)	Rifampicin (% resistant)	Ethambutol (% resistant)	Pyrazinamide (% resistant)
ACT (n = 30)	13.6	4.5	0	0
NSW (n = 472)	9.7	1.5	2.1	2.4
NT (n = 28)	4.5	0	0	0
Qld (n = 165)	11.4	4.9	1.4	4.2
SA (n = 48)	5.4	5	0	0
Tas (n = 9)	0	0	0	12.5
Vic (n = 448)	6.7	2	0.6	0.3
WA (n = 139)	7.5	2.8	0.9	3.8

National trends

Overall, rates of resistance have not changed significantly over the past decade. There has been a small trend upwards in the percentage of MDR-TB strains (resistance to at least isoniazid and rifampicin) (Figure 4.18). XDR-TB strains have remained rare (1 of 1027 strains tested in 2014).

Figure 4.18 Ten-year trends in resistance and multidrug-resistance patterns in Mycobacterium tuberculosis

XDR-TB = extremely drug-resistant tuberculosis

a Multidrug-resistant tuberculosis strains

Source: National Notifiable Diseases Surveillance system (public and private hospitals and health services)

Data table: Figure 4.18

Percentage of strains resistant to agents and combinations	2005 (n = 706)	2006 (n = 775)	2007 (n = 782)	2008 (n = 913)	2009 (n = 966)	2010 (n = 1023)	2011 (n = 1059)	2012 (n = 984)	2013 (n = 936)	2014 (n = 1027)
Isoniazid only	5.9	9.5	7.5	6.2	9.7	6.5	6.1	7.4	7.2	6.3
Rifampicin only	0.3	0.1	0.4	0.2	0.6	0.3	0.1	0.3	0.3	0.7
Isoniazid + rifampicin^a	0.8	1.4	1.4	1.3	1.6	1.3	1.7	1.4	1.1	0.7
Isoniazid + rifampicin + ethambutol^a	0.6	0.3	0.1	0.7	0.1	0.1	0.2	0.2	0.4	0.1
Isoniazid + rifampicin + pyrazinamide^a	0.1	0.0	0.9	0.3	0.8	1.6	0.2	0.1	0.2	0.3
Isoniazid + rifampicin + ethambutol + pyrazinamide^a	0.1	0.4	0.0	0.1	0.0	0.1	0.5	0.3	0.7	0.6
XDR-TB	0.0	0.0	0.0	0.0	0.0	0.2	0.0	0.0	0.0	0.1

Detailed reports of susceptibility data for M. tuberculosis from 1996 onwards can be found on the Australian Government Department of Health website. Guidelines for Australian mycobacteriology laboratories have been published in Communicable Diseases Intelligence (see Appendix 3).