Published Date: 2007-03-02 15:00:02
Subject: PRO/EDR> Tuberculosis, XDR, 1991-2003 - Spain
Archive Number: 20070302.0738
TUBERCULOSIS, XDR, 1991-2003 - SPAIN
A ProMED-mail post
ProMED-mail is a program of the
International Society for Infectious Diseases
Date: Thu 1 Mar 2007
From: ProMED-mail <firstname.lastname@example.org>
Source: Emerging Infectious Diseases (in press) [edited]
An emergency has been declared in KwaZulu Natal, South Africa, where an
outbreak of 53 cases of a highly lethal form of tuberculosis (TB) has
occurred (1,2). This outbreak was caused by an extensively drug-resistant
TB (XDR TB) strain.
XDR TB is defined as TB caused by _Mycobacterium tuberculosis_ isolates
resistant to isoniazid and rifampicin [also called rifampin. - Mod.LL] plus
any fluoroquinolone and one or more of the 3 injectable second-line drugs
(3). XDR TB may be considered an emerging disease but not a new disease.
Nosocomial outbreaks of multidrug-resistant TB (MDR TB) occurred in Spain
at the height of the HIV epidemic, when 49 TB cases were reported in an HIV
ward in Madrid, from 1991 through 1995 (4, 5). Molecular epidemiology found
that a particular strain caused 16 cases in another hospital in Madrid in
1993-1995 (6) and 31 cases in a hospital in Malaga in 1995-1998 (7,8).
In total, 22 hospitals from 6 different regions of Spain were affected by
this outbreak, which included at least 114 cases, caused by a _M. bovis_
XDR strain (B strain) belonging to the _M. tuberculosis_ complex. The
patients included one from the Netherlands (8) and another from Canada (9).
The strain responsible for the 1991-1995 outbreak in Spain fits the XDR TB
case definition; it was resistant to the 5 first-line drugs, as well as to
ofloxacin, aminosalicylic acid, cycloserine, ethionamide, capreomycin,
amikacin, and clarithromycin. Isolates were tested for drug susceptibility
by the Canetti method on Lowenstein-Jensen medium supplemented with
isoniazid, rifampicin, ethambutol, streptomycin, amikacin, and pyrazinamide
(6). The isolates were also tested on 7H10 Middlebrook agar for
susceptibility to aminosalicylic acid, ethionamide, capreomycin,
clarithromycin, and ofloxacin (6). No effective medical treatment was
available for these patients. In 2 of the hospitals affected, all patients
died, with a short survival time (median of 44 and 49.5 days for the 2
hospitals) between diagnosis and death (6, 7). A high rate of reinfection
(45 per cent) also was noted among HIV-positive patients treated with
anti-TB drugs (7).
As a result of this outbreak, Spanish hospitals now implement exhaustive
control measures, such as maintaining respiratory isolation units under
negative pressure; in addition, a national surveillance network for MDR TB
was set up in Spain in 1998. From 1998 through 2003, we detected 22 new
cases of infection with this strain (10), but no new cases have since been
reported to the national MDR TB database.
Our experience indicates that the implementation of more stringent control
measures and the use of new, more effective treatments for HIV infection
can help to bring XDR TB outbreaks under control in developed countries.
However, the outlook is bleak for developing countries like South Africa,
in which co-infection with HIV and a highly transmissible and untreatable
XDR TB strain could amplify the TB problem to levels unprecedented since
the advent of antimicrobial drugs. These countries urgently require
assistance with the establishment of control measures and the development
of new drugs and effective vaccines against TB.
1. Gandhi NR, Moll A, Sturm AW, et al. Extensively drug-resistant
tuberculosis as a cause of death in patients co-infected with tuberculosis
and HIV in a rural area of South Africa. Lancet 2006; 368: 1575-80.
2. Cohen J. Infectious disease. Extensively drug-resistant TB gets foothold
in South Africa. Science 2006; 313: 1554.
3. CDC. Revised definition of extensively drug-resistant tuberculosis. MMWR
Morb Mortal Wkly Rep 2006; 55: 1176.
4. CDC. Multidrug-resistant tuberculosis outbreak on an HIV ward - Madrid,
Spain, 1991-1995. MMWR Morb Mortal Wkly Rep 1996; 45: 330-3.
5. Rullan JV, Herrera D, Cano R, et al. Nosocomial transmission of
multidrug-resistant _Mycobacterium tuberculosis_ in Spain. Emerg Infect Dis
1996; 2: 125-9.
6. Guerrero A, Cobo J, Fortun J, et al. Nosocomial transmission of
_Mycobacterium bovis_ resistant to 11 drugs in people with advanced HIV-1
infection. Lancet 1997; 350: 1738-42.
7. Rivero A, Marquez M, Santos J, et al. High rate of tuberculosis
reinfection during a nosocomial outbreak of multidrug-resistant
tuberculosis caused by _Mycobacterium bovis_ strain B. Clin Infect Dis
2001; 32: 159-61.
8. Samper S, Martin C, Pinedo A, et al. Transmission between HIV-infected
patients of multidrug-resistant tuberculosis caused by _Mycobacterium
bovis_. AIDS 1997; 11: 1237-42.
9. Long R, Nobert E, Chomyc S, et al. Transcontinental spread of
multidrug-resistant. _Mycobacterium bovis_. Am J Respir Crit Care Med 1999;
10. Samper S, Iglesias MJ, Rabanaque MJ, et al. Spanish Working Group on
MDR-TB. Systematic molecular characterization of multidrug-resistant
_Mycobacterium tuberculosis_ complex isolates from Spain. J Clin Microbiol
2005; 43: 1220-7.
[byline: Sofia Samper, Carlos Martin]
[The in-press letter underscores an essential point related to XDR TB; that
is, that even though the infection is quite difficult to treat, aggressive
infection control procedures and modern anti-retroviral therapy can be
effective in limiting the spread of the infection in the hospital setting.
A further note, as pointed out by Dr Richard Frankel, rifampin is one of a
group of drugs called rifamycins and, outside of the USA, the drug is
usually called rifampicin. - Mod.LL]