Jornal Brasileiro de Pneumologia 3 0 (4 ) - Jul/ Ago de 2 0 0 4
Drug - re sistant
My co bacte rium tube rculo sis strains
isolated at an AIDS reference center general hospital in
Rio de Janeiro*
ROSSANA COIMBRA BRITO, CELINE GOUNDER, DIRCE BONFIM DE LIMA, HÉLIO SIQUEIRA, HEBE RODRIGUES CAVALCANTI, MARACY MARQUES PEREIRA, AFRÂNIO LINEU KRITSKI(TE SBPT)
Background: Tuberculosis become important challenge to health care settings. Brazil has high prevalence of the disease and Rio de Janeiro has high incidence rates with 30% of cases notified at hospitals.
Objective: To evaluate prevalence of initial and acquired drug resistance at a general hospital, reference for aids treatment in Rio de Janeiro and to identify associated factors.
Methods: Mycobacterium tuberculosis strains from 165 patients were analyzed, between August 1996 and February 1998.
Results: Twen t y per cen t (33/ 165) were resist an t t o at least on e dru g; 13% (12/ 165) t o ison iazid; 3.64% (6/ 165) t o rifampin an d 3.64% (6/ 165) t o bot h. Amon g HIV seroposit ive su bject s (52/ 165); 28.85% (15/ 52) were resist an t t o at least on e dru g. Acqu ired resist an ce occu rred in 15.79% of 19 pat ien t s t hat men t ion ed previou s an t iTB t reat m en t . Associat ion st at ist ically sign ifican t was fou n d wit h n on cavit at ion on X- ray in bivariat e an alyses (P=0.05). Eight y fou r pat ien t s refereed n o previou s t reat men t (NPT). Resist an ce t o 1 or more dru gs was fou n d in 2 8 .5 7 % (2 4 / 8 4 ) o f NPT p at ien t s. Asso ciat io n st at ist ically sig n ifican t wit h in it ial resist an ce was fo u n d wit h healt h care workers (P=0.004), u n employmen t (P=0.03), an d diarrhea (P=0.01) in bivariat e an alyses. On mu lt ivariat e an alyses, healt h care workers (P=0.002) remain ed sign ifican t ly associat ed wit h in it ial resist an ce.
Co nclusio ns: High resist an ce rat es was fou n d. It corroborat es t hat hospit als n eeds at t en t ion for TB con t rol especially which concerns to health care works infection.
Key w o rds: Mycobact eriu m t u bercu losis. Dru g resist an ce. Disease t ran smission , pat ien t t o profession al. Hospit als.
* St u dy carried ou t at t he Un iversidade Federal do Rio de J an eiro (Rio de J an eiro Federal Un iversit y).
Fin an cial su pport : Rede Brasileira de Pesqu isa em TB (Rede- TB, Brazilian Tu bercu losis Research Net work)/ Processo 62.0055/ 01- 4- PACDT- Milen io
SINAN – Sist ema de In formações de Agravos de Not ificação
(Case- regist ry dat abase) TB – Tu bercu losis Approximat ely 95% of t hese cases, an d 98% of
TB- relat ed deat hs, have occu rred in developin g cou n t ries(2).
Accordin g t o t he World Healt h Organ izat ion , Brazil ran ks fift een t h am on g n at ion s wit h t he h ig h est rat es o f TB.(1 ) In 2 0 01 , t h ere were an
est im at ed 111,000 n ew cases of t he disease, for a n in cid en ce ra t e o f 6 4 / 1 0 0 ,0 0 0 in h a b it a n t s. Con t rol of t he disease is poor in variou s region s o f t h e co u n t ry, a n d t h e im p le m e n t a t io n o f su p ervised t rea t m en t st ra t eg ies is st ill in t h e in cip ien t p h a se(1 ). In 1 9 9 9 , t h e cu re ra t e wa s
7 5 . 4 0 % , a n d t h e re w a s a 1 3 . 81 % ra t e o f n on complian ce wit h t reat men t . Over t he past few years, t he highest n egat ive im pact on TB con t rol h a s o ccu rred in la rg e cit ies – a s a resu lt o f wo rsen in g so cio eco n o m ic co n d it io n s a n d t h e dism an t lin g of t he healt h syst em . Dat a are m ore alarmin g in t he sou t heast ern part of t he cou n t ry, where co- infection with human immunodeficiency viru s (HIV) is t he highest .(3 )
There are approxim at ely 6 m illion people in the city of Rio de Janeiro, the largest metropolitan area in t he st at e of Rio de J an eiro. In 2000, 9223 TB cases were report ed (6680 n ew cases), for an in ciden ce rat e of 114/ 100,000 in habit an t s, an d t he mort alit y rat e was 6.53%.(4) In 1995, on e t hird
of t he 9500 TB cases report ed in t he cit y of Rio d e J a n eiro o ccu rred in h o sp it a ls, wh ere m o st report ed TB/ HIV co- in fect ion cases (63%) also occu rred.(5 )
Prim a ry a n d a cq u ired resist a n ce t o a n t i- TB d ru g s h a s b een rep o rt ed sin ce t h e in t ro d u ct io n o f a n t im icro b ia l d ru g s fo r TB t re a t m e n t .(6 ,7 )
Developed cou n t ries have been con cern ed abou t t h e in crease o f p rim ary an d acq u ired resist an ce, esp ecia lly in la rg e u rb a n a rea s. Mo st ca ses o f p rim a ry resist a n ce a re ca u sed b y co n t a m in a t io n o f in d o o r e n viro n m e n t s (h o sp it a ls, p riso n s, shelt ers) an d HIV co- in fect ion .(8 - 1 0 ) Very few dat a
h a ve b een co llect ed co n cern in g t h is su b ject in d e ve lo p in g co u n t rie s. On t h e o n e h a n d , TB co n t ro l p ro g ra m s h a ve em p h a sized t h e u se o f
sp u t u m sm ea r m icro sco p y in p a t ien t s t rea t ed in b a sic h ea lt h u n it s. On t h e o t h er h a n d , t h ere a re n o gu idelin es for t he u se of mycobact eria cu lt u re a n d su scep t ib ilit y t est s in p a t ien t s t rea t ed in g en era l h o sp it a ls.(11 ,1 2 )
It is b elieved t h a t resist a n ce h a s a lso b een in creasin g in d evelo p in g co u n t ries, esp ecially in la rg e u rb a n cen t ers, if we co n sid er t h e h ig h in cid en ce o f n o n co m p lian ce wit h t reat m en t an d t h e h i g h n u m b e r o f p a t i e n t s t r e a t e d i n h o sp it a ls.(1 2 ) Sin ce t h e re a re fe w re p o rt s o n
p rim a ry resist a n ce in t h ese co u n t ries, esp ecia lly in en viro n m en t s su ch a s h o sp it a ls a n d p riso n s (wh ere h ig h er in cid en ce is exp ect ed ), su rveys h a ve b een p erfo rm ed in o rd er t o ch a ra ct erize d ru g - resist an ce p ro files.(1 3 - 1 5 )
There are very few dat a on resist an ce t o an t i-TB dru gs in ou r cou n t ry. A m u lt icen t er st u dy performed by the Ministry of Health between 1995 an d 1996 showed a prim ary resist an ce rat e of 8.5% an d an acqu ired resist an ce rat e of 21.0%. Prim ary resist an ce t o t he rifam pin an d ison iazid com bin at ion (RIF+INH) occu rred in 1.1% of t he cases st u d ied , an d acq u ired resist an ce t o t h is combin at ion was 7.9%. The pat ien t s in t hat st u dy had not been submitted to anti- HIV serology tests. In addit ion , pat ien t s t reat ed in hospit als were n ot included in the study in a representative fashion.(7)
Jornal Brasileiro de Pneumologia 3 0 (4 ) - Jul/ Ago de 2 0 0 4
Wit h t he decon st ru ct ion of t he t reat m en t of p a t ien t s d ia g n o sed wit h TB – ca u sed b y t h e dism an t lin g of TB con t rol program s in variou s cit ies an d t he presen ce of a con siderable n u mber of pu blic hospit als in t he cit y of Rio de J an eiro – pat ien t s u su ally go t o hospit als for diagn osis an d t reat men t of TB in st ead of visit in g primary healt h u n it s.(1 7 ) In addit ion t o t his, som e com plex cases,
su ch as t hose wit h acqu ired im m u n odeficien cy syn d ro m e (AIDS) o r o t h er co m o rb id it ies, a re referred to hospitals. Since there are no TB control p ro g ra m s in h o sp it a ls, t h ere a re n o d a t a o n t re a t m e n t o u t co m e s (n o n co m p lia n ce , cu re , mort alit y, side effect s) or st rain resist an ce t o an t i-TB dru gs. On ly t wo hospit als in t he cit y of Rio de J an eiro have been cu rren t ly su bm it t in g pat ien t s t o m ycobact eria cu lt u re as a rou t in e procedu re, bu t n on e have been perform in g an t i- TB dru g su scept ibilit y t est s.(1 8 ) Recen t st u dies have shown
high prim ary m u lt idru g- resist an t rat es (15% in HIV- posit ive pat ien t s an d 3% in HIV- n egat ive pat ien t s) at a referen ce cen t er gen eral hospit al in t he cit y of Rio de J an eiro, an d a great n u m ber of p o sit ive t u b ercu lin t est resu lt s (8 .7 %) a m o n g healt h care profession als.(2 0 )
The objective of the present study was to evaluate prevalence of primary and acquired drug resistance and to identify associated risk factors. In order to do so, we studied resistance to anti- TB drugs in Mt b st rain s iso lat ed fro m p at ien t s at an o t h er reference center general hospital over an 18- month period.
METHOD
A t ra n sversa l st u d y wa s ca rried o u t fro m Au g u st 1 9 9 6 t o Feb ru a ry 1 9 9 8 . Cu lt u res fo r m yco b a ct e ria w e re re q u e st e d b y a t t e n d in g p h ysicia n s a n d a n a lyzed in t h e m icro b io lo g y la b o ra t o ry a t t h e Ho sp it a l Un iversit á rio Ped ro Er n e s t o (HUP E, P e d r o Er n e s t o Un ive r s it y Ho sp it a l) o f t h e Un iversid a d e d o Est a d o d o Rio d e J a n eiro (Rio d e J a n eiro St a t e Un iversit y). All cu lt u res t est in g p o sit ive wit h in t h is p erio d were s e le c t e d . All s a m p le s w e r e s u b m it t e d t o su scep t ib ilit y t est s an d , wh en p o ssib le, p at ien t s were in t erviewed . Med ica l reco rd s o f a ll ca ses select ed were a n a lyzed u sin g a st a n d a rd ized fo rm . Th ese p ro ced u res a llo wed d em o g ra p h ic, clin ica l, a n d la b o ra t o ry a n a lysis d a t a t o b e co llect ed . Th e HUPE is a t ert ia ry- ca re g en era l
hospit al, t reat in g in pat ien t s an d ou t pat ien t s. The co m p lex in co rp o ra t es clin ics, in firm a ries, a n d in t en sive ca re u n it s, a n d a ct ivit ies t a rg et ed a t t h e ed u ca t io n o f h ea lt h ca re p ro fessio n a ls a re a lso d evelo p ed . It is a lso a referen ce cen t er fo r p a t ien t s wit h HIV/ AIDS, a n d is lo ca t ed in t h e Vila Iza b el d ist rict , in t h e m et ro p o lit a n a rea o f t h e cit y o f Rio d e J a n eiro . Nevert h eless, t h is h o sp it a l receives p a t ien t s fro m o t h er d ist rict s, o t h e r c it ie s (e s p e c ia lly f r o m t h e b a ix a d a flu min en se, or “lower Rio” region ) an d even from o t h er st a t es. Th e a n n u a l n u m b er o f p a t ien t s d ia g n o sed wit h TB h a s b een a p p ro xim a t ely 3 5 0 fo r t h e p a st few yea rs. At t h e t im e o f t h e st u d y, t h ere were 6 0 4 p a t ien t b ed s in t h e HUPE, yet t h ere were n o b ed s d esig n a t ed fo r resp ira t o ry iso la t io n o r TB co n t ro l a ct ivit ies.
All posit ive cu lt u res of st rain s isolat ed du rin g t h e st u d y p erio d a n d co n firm ed a s Mt b t h ro u g h b io ch em ica l t est s were in clu d ed in t h e st u d y. Exclu sio n crit eria in clu d ed co n t a m in a t io n o f cu lt u re m a t eria l a n d t ech n ica l p ro b lem s t h a t affect ed su scep t ib ilit y t est resu lt s.
Dire ct e xa m in a t io n o f m yco b a ct e ria wa s p erfo rm ed u sin g t h e Zieh l- Neelsen m et h o d , an d t h e cu lt u re m ed iu m u sed fo r m yco b a ct eria wa s Lö we n st e in - J e n se n , in a cco rd a n ce wit h t h e g u id e lin e s re co m m e n d e d in t h e Ma n u a l d e Bact erio lo g ia d a Tu b ercu lo se d o Min ist ério d a Sa ú d e (H e a l t h M i n i s t r y Gu i d e b o o k f o r Tu bercu losis Bact eriology)(2 1 ). At t he Laborat ório
Noel Nu t t els, a st at e referen ce laborat ory for t he b a c t e r io lo g ic a l d ia g n o s is o f TB, Mt b w a s id en t ified (t h ro u g h t h e verificat io n o f g ro wt h in t he presen ce of t he in hibit ors TCH an d PNB) an d su scep t ib ilit y t est s were p erfo rm ed (Can et t i an d Grosset proport ion m et hod), bot h in accordan ce wit h t h e g u id elin es reco m m en d ed in t h e Hea lt h Min ist ry Gu id eb o o k.(2 1 )
RESULTS
Du rin g t he st u dy period, 380 cases of TB were report ed at HUPE. A t ot al of 165 st rain s (isolat ed from 165 pat ien t s) met t he in clu sion crit eria. Two s a m p le s c h a r a c t e r iz e d a s n o n t u b e r c u lo u s m yco b a ct eria were exclu d ed . Th ere were n o exclu sio n s d u e t o co n t am in at io n o r t ech n ical problems. The medical records of all part icipat in g pat ien t s were reviewed in order t o gat her clin ical an d epidemiological dat a, which were in clu ded in t he an alysis. In addit ion , 110 of t he 165 pat ien t s were in t erviewed . Th ere were n o st a t ist ica lly sig n ifica n t d iffe re n ce s in so cio d e m o g ra p h ic characteristics, clinical presentation of TB, gender, age, HIV posit ivit y or hospit alizat ion bet ween interviewed patients and those for whom data was obt ain ed solely from medical records.
Twen t y- five pat ien t s (15%) were less t han 20 years of age, 77 (46%) were bet ween 20 an d 40, 46 (29%) were bet ween 40 an d 60, an d 17 (10%) were o ld er t h an 6 0 . On e h u n d red an d eleven p a t ie n t s (6 7 % ) w e re m a le . Th e re w e re 7 7 Caucasians (47%) and 58 non- whites (35%). Fifty-six pat ien t s (34%) report ed havin g had less t han 8 years of schoolin g, an d 103 (63%) report ed havin g complet ed at least 8 years. On e hu n dred and forty- seven patients (89%) were employed and 17 (10%) were u n employed. Twen ty- fou r patien ts (14.5%) reported previous anti- TB treatment (data were co n sist en t b et ween m ed ical reco rd s an d in t erview n ot es). Of t he 113 pat ien t s su bmit t ed t o HIV t est in g, 52 (46%) t est ed posit ive. Thirt y- six (22%) pat ien t s report ed havin g con t act wit h a TB pat ien t in t he home. Seven pat ien t s (4%) were healt h care profession als. Seven t y- t wo pat ien t s (44%) were hospit alized at t he t ime of diagn osis an d 86 (52%) were diagn osed as ou t pat ien t s. The most common clin ical presen t at ion was t ypical pulmonary TB (95 patients – 56%). Of the patients studied, 59 (48%) presented with a positive sputum sm ea rs were seen in 5 9 (4 8 % ), 1 4 o f wh o m presen t ed wit h st rain s resist an t t o some of t he
were resistant to INH, 17 (10.3%) to streptomycin, 6 (3.6%) t o RIF, 3 (1.8%) t o et hambu t ol, an d 6 (3.6%) to the RIF+INH combination. Of the 52 HIV/ AIDS p a t ien t s, 1 5 (2 8 .8 5 % ) p resen t ed st ra in s resist an t t o at least on e dru g. Primary resist an ce was det ect ed in 26 of 141 pat ien t s (18.4%) an d a cq u ire d re sist a n ce in 3 o f 2 4 (1 2 .5 % ). We reviewed dat a from t he Sist ema de In formações de Agravos de Not ificação (SINAN, Case- regist ry dat abase) for t he st at e of Rio de Jan eiro in order t o con firm whet her t he pat ien t s in clu ded as n ever previously submitted to anti- TB treatment had ever b een reg ist ered in t h e d at ab ase. No n e o f t h e patients participating in the present study had been previou sly regist ered in t he SINAN.
In the univariate analysis, general resistance to antimicrobial drugs was significantly correlated with bein g a healt h care profession al (p = 0.0007). Dist ribu t ion of t he main variables u n der st u dy in relat ion t o t he occu rren ce of gen eral resist an ce is fou n d in Table 1. Amon g pat ien t s wit h previou s anti- TB treatment, only cavitation- free chest X- rays showed a st at ist ically sign ifican t correlat ion wit h dru g resist an ce, wit h an odds rat io (OR) of 0.15 an d a 95% con fiden ce in t erval (95% CI) of 0 t o 1 .6 6 (p = 0 .0 5 ). Am o n g p a t ie n t s wh o we re t re a t m e n t n a ive , b iva ria t e a n a lysis sh o w e d st at ist ically sign ifican t correlat ion s bet ween dru g resist an ce an d t he followin g variables: bein g a healt h care profession al (OR = 18.16; 95% CI = 1.80 to 870.66; p = 0.004), diarrhea at the time of diagn osis (OR = 4.06; 95% CI = 1.19 t o 13.94; p = 0.01) an d u n employmen t (OR = 4.76; 95% CI = 0.92 t o 25.77; p = 0.03).
Jornal Brasileiro de Pneumologia 3 0 (4 ) - Jul/ Ago de 2 0 0 4
TABLE 1
Distribution of principal sociodemog raphic, epidemiolog ical, radiog raphic and clinical characteristics, in accordance w ith the finding of g eneral resistance
Ch a ra ct erist ic Resist a n t Su scep t ib le OR 95% CI p To t a l Gen d er
Fe m a le 8 3 8 0 .7 2 0.26 – 1.85 0 .61 4 6
Ma le 2 5 8 6 — — — 111
No dat a 0 8 0 .0 0 0.00 – 2.18 0 .2 0 8 Ag e
0- 19 years 3 2 2 — — — 2 5
20- 39 years 1 5 6 2 1 .7 7 0 .4 4 – 10 .41 0 .5 5 7 7 40- 59 years 11 3 5 2 .3 0 0 .5 2 – 1 4 .1 4 0 .3 5 4 6 60- 79 years 3 11 2 .0 0 0 .2 2 – 1 7 .2 2 0 .6 5 1 4 80- 99 years 1 2 3 .6 7 0 .0 5 – 8 8 .3 5 0 .3 8 3 Ra ce
No n - wh it e 1 4 4 4 1 .3 2 0.53 – 3.25 0 .6 6 5 8
Ca u ca sia n 1 5 6 2 — — — 7 7
No dat a 4 2 6 0 .6 4 0.14 – 2.27 0 .6 4 3 0 Sch o o lin g
≤8 ye a rs 1 0 4 6 0 .8 5 0.33 – 2.08 0 .8 6 5 6
>8 years 2 1 8 2 — — — 1 0 3
No dat a 2 4 1 .9 5 0 .1 6 – 1 4 .61 0 .6 0 6 Occu p a t io n
Un e m p lo ye d 6 11 2 .4 2 0.67 – 7.88 0 .11 1 7
Em p lo ye d 2 7 1 2 0 — — — 1 4 7
No dat a 0 1 0 .0 0 0 .0 0 – 1 7 4 .7 8 1 .0 0 1 Healt h care p ro fessio n al
Ye s 6 1 2 4 .2 7 2 .6 4 – 11 2 8 .3 7 0 .0 0 07 7
No 2 2 8 9 — — — 111
No dat a 5 4 2 0 .4 8 0.13 – 1.43 0 .2 4 4 7 Ho sp it a l st a t u s
In p a t ie n t 1 4 5 8 0 .91 0.38 – 2.14 0 .9 7 7 2
Ou t p a t ie n t 1 8 6 8 — — — 8 6
No dat a 1 6 0 .6 3 0.01 – 5.75 1 .0 0 7 Sm o kin g
Ye s 2 0 5 9 1 .7 7 0.69 – 4.83 0 .2 8 7 9
No 9 4 7 — — — 5 6
No dat a 4 2 6 0 .8 0 0.16 – 3.25 1 .0 0 3 0 Alco o lism o
Ye s 9 4 5 0 .61 0.22 – 1.57 0 .3 7 5 4
No 2 0 61 — — — 81
No dat a 4 2 6 0 .4 7 0.11 – 1.61 0 .3 0 3 0 Clin ica l p resen t a t io n
Pu lm o n a ry 1 8 7 7 0 .6 6 0.27 – 1.69 0 .4 5 9 5
Ot h er 1 2 3 4 — — — 4 6
No dat a 3 2 1 0 .4 0 0.07 – 1.77 0 .31 2 4 Chest X- ray
Ot her forms 1 4 4 2 1 .2 0 0.34 – 4.90 0 .9 9 5 6
Ca vit a t io n 5 1 8 — — — 2 3
No dat a 1 4 7 2 0 .7 0 0.20 – 2.82 0 .5 4 8 6 HIV serology
HIV- p o sit ive 1 3 3 9 1 .2 3 0.46 - 3.25 0 .81 5 2
HIV- n eg a t ive 1 3 4 8 — — — 61
No t t est ed 2 7 1 .0 5 0.10 - 6.51 1 .0 0 9 No dat a 5 3 8 0 .4 9 0.13 - 1.63 0 .31 4 3
Previo us anti- TB treatment
Yes (ret reat m en t ) 3 2 1 0 .4 6 0.08 – 1.75 0 .3 5 2 4
No 2 6 8 4 — — — 11 0
No dat a 4 2 7 0 .4 8 0.11 – 1.57 0 .3 0 31
The fin din gs of t he presen t st u dy u n derscore t he import an ce of givin g in creased at t en t ion t o TB in hospit als. We n ot iced a sociodemographic, clinical, and laboratory test result distribution that rarely differed from SINAN data. The great number of pat ien t s wit h t ypical pu lmon ary TB (95%) an d posit ive spu t u m smear resu lt s (58%), as well as t he proport ion diagn osed du rin g hospit alizat ion (72%), in dicates that the poten tial for n osocomial t ra n sm issio n is very h ig h . Th is is even m o re worrisome if we con sider t he fact t hat , in t he hospital under study, procedures recommended for decreasin g TB t ran smission risk were n ot bein g followed at t he t ime of t he st u dy.(22)
Ou r fin din g t hat primary resist an ce was 18.4% differs sign ifican t ly from t he rat e report ed (8.5%) in t he most recen t n at ion al su rvey carried ou t in p rim a ry c a re u n it s.(7 ) P a rt ic u la rit ie s in t h e
popu lat ion t reat ed in hospit als may in crease t he in cid en ce o f resist an t st rain s. Co - m o rb id it ies, in clu din g HIV co- in fect ion , an d diseases t hat are difficu lt t o diagn ose or t reat may be examples of su ch fact ors.
Th e a n t i- TB d r u g r e s is t a n c e r a t e t h a t comman ded t he most at t en t ion was t hat relat ed t o INH (13.3%). This is t he dru g most common ly e m p lo ye d in TB t re a t m e n t a n d p ro p h yla xis regimen s. Resist an ce t o t he RIF+INH combin at ion was 3.6% in ou r st u dy, approximat ely t hree t imes higher t han t hat fou n d in t he n at ion al su rvey an d similar to that described in another general hospital in t h e cit y o f Rio d e J a n eiro .1 9 Th is t yp e o f
resist an ce mu st be closely mon it ored becau se of the serious consequences for control of the disease. The on ly variable t hat correlat ed sign ifican t ly wit h acqu ired resist an ce was cavit at ion - free chest X- ray. It is import an t t o highlight t hat , in t he sample studied, the number of patients presenting secondary resistance was very low (only 3 patients). This fin din g differs great ly from t hat of ot her st u dies in t he lit erat u re, in which t he in ciden ce of pat ien t s presen t in g wit h acqu ired resist an ce is usually much higher than that of those presenting
b iva ria t e a n a lysis, a n d a p p ea red a g a in in t h e m u lt iva ria t e a n a lysis. Th is is h ig h ly releva n t . Although the odds ratios were high and statistically significant, similar studies in other hospitals should be carried out. If these findings are confirmed, they will lead u s t o re- evalu at e t he well- kn own risks of infection that health care professionals have to face an d t o recon sider t he fin din gs on n osocom ial t ran smission of resist an t st rain s report ed in t he lit e ra t u re .(2 5 - 2 7 ) We ca n co n clu d e t h a t h e a lt h
professionals are more likely to be infected by Mtb t han t he popu lat ion in gen eral, an d t hat t here are more resistant strains circulating in hospitals such a s t h a t o f t h e p re se n t st u d y, wh e re co n t ro l m e a s u re s a re p o o r. Th e re f o re , h e a lt h c a re profession als are defin it ely exposed t o sign ifican t risks, an d specific gu idelin es for prot ect in g t hese p ro fe ssio n a ls m u st b e e st a b lish e d b y t h o se responsible for set t in g pu blic healt h care policy.
In the bivariate analysis, we found a correlation bet ween primary resist an ce an d diarrhea, as well as between primary resistance and unemployment, b u t t h ese co rrelat io n s were n o t fo u n d in t h e mu lt ivariat e an alysis. These may be con fou n din g variables. Therefore, these findings would be better charact erized in st u dies wit h larger samples.
Another aspect that must be highlighted is that t h ere wa s n o sig n ifica n t co rrela t io n b et ween resist an ce an d HIV in fect ion , alt hou gh 28.85% of t he pat ien t s wit h HIV/ AIDS presen t ed resist an t st rain s. This fin din g corroborat es t hat of a st u dy performed in an ot her Rio de Jan eiro hospit al wit h a profile similar t o t hat of HUPE.(8- 10) The au t hors
of t hat st u dy report ed resu lt s t hat also deviat ed fro m t h e t ren d d escrib ed in t h e in t ern at io n al lit erat u re. Nevert heless, t his may be du e t o t he smaller n u mber of pat ien t s presen t in g wit h HIV co- infection when compared to those who are not in follow- up treatment for multidrug- resistant TB in t he st at e of Rio de Jan eiro.(16) The possibilit y
Jornal Brasileiro de Pneumologia 3 0 (4 ) - Jul/ Ago de 2 0 0 4
co- in fect ion an d su scept ibilit y profile, as shown in a recen t st u dy on mort alit y cau sed by TB in hospit als in t he st at e of Rio de Jan eiro (very few mycobacteria cultures, susceptibility tests and anti-HIV t est s had been requ est ed for pat ien t s who su bsequ en t ly died).(26)
An ot her aspect t hat deserves at t en t ion was highlighted in a study by Salles et al., who reported a high rat e of n on complian ce (26%) in pat ien t s treated in a general hospital that had no TB control program in place.(27) This finding provides evidence
t hat pat ien t s wit h resist an t st rain s are more likely t o be fou n d in su ch en viron men t s.
In a review of t he lit erat u re, McGowan Jr (28)
d e m o n s t ra t e d t h a t t h e a t t e n t io n g ive n t o n o so co m ial TB is a react io n t o t h e in creased n u mber of cases in t he commu n it y. Therefore, t he problem with hospitals cannot be dissociated from the epidemiological reality of TB in the community. Assessin g t he impact of TB an d implemen t in g control measures in hospitals should be considered p rio rit ies, esp ecia lly in a rea s wh ere t h e t o t a l n u mber of cases is in creasin g an d t here are high rat es of n on complian ce wit h t reat men t an d high in ciden ce of resist an t st rains. Moreover, we must bear in min d t hat t his in crease is clearly more pronounced within population subgroups of those who are more likely t o be hospit alized, su ch as patients with AIDS or other debilitating diseases.(28)
The lack of appropriat e biosafet y measu res t o reduce the risk of TB infection in hospitals, as well as the presence of resistant strains, make hospitals an environment in which resistant strains are more likely to be identified and disseminated. Therefore, health care professionals and patients are exposed n ot on ly t o Mt b bu t also t o resist an t st rain s of Mtb.
Th e re co m m e n d a t io n s f o r TB co n t ro l in hospit als in clu de: t he est ablishmen t of a special commit t ee respon sible for con t rol; an act ion plan t h a t is p e rio d ic a lly re vise d ; id e n t if ic a t io n , e va lu a t io n , a n d e a rly t re a t m e n t o f p a t ie n t s diagn osed wit h act ive TB; en viron men t al con t rol; respiratory protection ; con tin u in g edu cation ; an d in t egrat ion wit h pu blic healt h organ izat ion s.(22)
Blu mberg et al. st u died t he effect iven ess of introducing such measures in a hospital in Atlanta, Georgia (USA) an d report ed a decrease in t he n u mber of n ew cases amon g in dividu als exposed t o t he disease an d in t he n u mber of posit ive PPD
t est s a m o n g h ea lt h ca re p ro fessio n a ls.(2 9 ) Th e
a u t h o r s a ls o s u g g e s t e d t h a t c h a n g e s in admin ist rat ive policies played t he most import an t role in achievin g su ccess, in dicat in g t hat t hese shou ld be t he first modificat ion s implemen t ed in su ch an at t empt t o improve con t rol measu res.
In 1996, Mu zzy de Sou za et al. report ed t hat gen eral hospit als were t he most likely places for TB t ra n sm issio n t o o ccu r.2 9 Acco rd in g t o t h e
authors, hospitals presenting the highest risk would be those which: treat more than 50 TB cases/ year; a re re f e re n ce ce n t e rs f o r t h e t re a t m e n t o f immunosuppressed patients (HIV- positive or not); have a high n u mber of healt h care profession als younger than 29; are also university hospitals (with u n dergradu at e an d gradu at e st u den t s); make u se of cert ain diagn ost ic an d t herapeu t ic procedu res (such as bronchoscopy, orotracheal intubation and spu t u m in du ct ion ); have adopt ed n o TB con t rol programs or biosafet y measu res.
In conclusion, we must take into consideration t he limit at ion s of st u dies su ch as t he presen t on e. Ou r st u dy was rest rict ed t o a sin gle healt h care entity, having its own particularities, some of them t ra n sit ive . Ho we ve r, o u r re su lt s h ig h lig h t a pot en t ially seriou s sit u at ion t hat shou ld also be investigated in other hospitals with similar profiles. In addit ion , t he dist ribu t ion of cases in hospit als located in large urban centers with profiles similar t o t hat of Rio de Jan eiro shou ld be evalu at ed t h ro u g h su rve ys in o rd e r t o d e t e rm in e t h e in c id e n c e a n d p re va le n c e o f a n t i- TB d ru g resistance.
ACKNOWLEDGMENTS
We wo u ld like t o t h a n k t h e st a ffs o f t h e Department of Infectious and Parasite Diseases, the Ho sp it a l In f e ct io n Co n t ro l Co m m it t e e , t h e Mycobact eria Laborat ory of HUPE, an d t he HIV Research Laborat ory of t he Un iversidade Federal do Rio de Jan eiro.
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