Nebulized colistin treatment of multi

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Med Int ensiva. 2011;35(4):226−231
medicina intensiva
www.elsevier.es/ medint ensiva
ORIGINAL
Nebulized colistin treatment of multi-resistant Acinet obact er
baumannii pulmonary infection in critical ill patients
M.J. Pérez-Pedrero, M. Sánchez-Casado,* S. Rodríguez-Villar
Servicio de Medicina Int ensiva, Complej o Hospit alario de Toledo, Toledo, Spain
Received 14 Oct ober 2010; accept ed 19 January 2011
KEYWORDS
Colist in;
Nebulized colist in;
Mult i-resist ant germs;
Acinet obact er
baumannii
Abstract
Obj ect ive: To analyze t he efficacy of nebulized colist in in t he microbiological eradicat ion and
clinical improvement of pat ient s wit h pulmonary inf ect ion by mult i-resist ant Acinet obact er
baumannii (MAB).
Design: A ret rospect ive st udy.
Set t ing: Int ensive Care Unit of a Tert iary hospit al.
Pat ient s: Hospit alized pat ient s on invasive mechanical vent ilat ion wit h posit ive MAB cult ures of
t he airway.
Int er vent i ons: Al l received t reat ment wit h col ist in (CL). Nosocomial pneumonia (NP) or
Tracheobronchit is (TB) was det ermined according t o rout ine crit eria and colonizat ion (CO) was
det ermined in t he case of a posit ive cult ure in t he absence of infect ion crit eria. Three groups of
pat ient s were defined: t hose t reat ed wit h nebulized CL, t hose t reat ed wit h IV CL and t hose
t reat ed wit h IV CL plus nebulized CL.
Main measurement s: Baseline charact erist ics. Microbiological eradicat ion and clinical recovery
were evaluat ed according t o rout ine crit eria.
Result s: 83 pat ient s were st udied, 54 of whom were t reat ed, wit h t he following diagnoses: 15
(27.8%) wit h NP, 16 (29.6%) wit h TB and 23 pat ient s (42.6%) wit h CO. Nebulized CL was used in
36 pat ient s (66.7%): 66.7%of which for CO, 33.3%in t reat ment for TB and in no case of NP. In
61.1%of t he pat ient s, IV CL was used: 22.2%of which for CO, 38.9%for TB and 38.9%in NP. The
combinat ion of IV CL and nebulized CL was used in 15 pat ient s (27.8%): 5 pat ient s (33.3%) CO, 2
pat ient s (13.3%) TB and 8 pat ient s (53.3%) NP. Microbiological eradicat ion was achieved in 32
pat ient s (59.3%), wit h t he following dist ribut ion: 8 (47.1%) wit h IV CL, 15 (83.3%) wit h nebulized
CL and 9 pat ient s (69.2%) wit h a combinat ion of IV CL and nebulized CL. Clinical recovery was
achieved in 42 pat ient s (77. 8%): 12 (80%) wit h IV CL, 18 (94. 7%) wit h nebulized CL and 12
(85.7%) wit h a combinat ion of nebulized and IV CL. These differences were not significant . In
*Corresponding aut hor.
E-mail address: marcel55@t erra.es (M. Sánchez-Casado).
0210-5691/ $ - see front mat t er © 2010 Elsevier España, S.L. and SEMICYUC. All right s reserved.
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Nebulized colist in t reat ment of mult i-resist ant Acinet obact er baumannii pulmonary infect ion in crit ical ill pat ient s
227
t he group of pat ient s wit h inf ect ion due t o TB and NP (31 pat ient s, 57. 4%), microbiological
eradicat ion was achieved in 5 pat ient s (100%) t reat ed wit h nebul ized CL and in 6 of t he
9 pat ient s (42.9%) t reat ed wit h IV CL, t he difference being significant (P < .05). Clinical recovery
in t his group was 100%(6 pat ient s) t reat ed wit h nebulized CL and 75%(9 of t he 12 pat ient s) in
t he IV CL group. This difference was not significant .
Conclusions: Our st udy suggest s t hat t reat ment wit h colist in in pat ient s wit h pulmonary infect ion
wi t h mul t i -resi st ant Aci net obact er baumanni i coul d be more ef f i ci ent i f i t were t o be
administ rat ed solely nebulized or in combinat ion wit h IV colist in rat her t han administ ered solely
int ravenously.
© 2010 Elsevier España, S.L. and SEMICYUC. All right s reserved.
PALABRAS CLAVE
Colist ina;
Colist ina nebulizada;
Microorganismos
mult irresist ent es;
Acinet obact er
baumannii
Utilización de la colistina nebulizada en la colonización e infección respiratoria
por Acinet obact er baumannii en pacientes críticos
Resumen
Obj et ivo: Evaluar la eficacia de la colist ina nebulizada en la erradicación microbiológica y la
mej oría clínica de pacient es con Acinet obact er baumannii en vías respirat orias.
Diseño: Est udio ret rospect ivo.
Ámbit o: Servicio de medicina int ensiva en hospit al t erciario.
Pacient es: Pacient es ingresados en vent ilación mecánica invasiva con cult ivos posit ivos en vía
aérea para A. baumannii mult irresist ent e.
Int ervenciones: Todos recibieron t rat amient o con colist ina (CL). Se det erminó neumonía nosocomial (NN) o t raqueobronquit is (TB) según crit erios habit uales y colonización (CO) si había
cult ivo posit ivo en ausencia de crit erios de infección. Se definieron 3 grupos de pacient es: t rat ados con CL nebulizada, con CL i.v. y con CL i.v. más nebulizada.
Variables de int erés: Caract eríst icas basales. Se consideró erradicación microbiológica y curación clínica según crit erios habit uales.
Result ados: Se est udió a 83 pacient es; 54 fueron t rat ados, con los diagnóst icos: 15 (27,8%) con
NN, 16 (29,6%) con TB y 23 pacient es (42,6%) con CO. La CL nebulizada fue ut ilizada en 36 pacient es (66,7%): en el 66,7%en CO, el 33,3%en t rat amient o de TB y en ningún caso de NN. En el
61,1%de los pacient es se ut ilizó CL i.v.: en la CO en el 22,2%, en la TB en el 38,9%y en las NN
en el 38,9%. La combinación de CL i.v. más nebulizada fue ut ilizada en 15 pacient es (27,8%), que
se empleó: 5 (33,3%) CO, 2 (13,3%) TB y 8 (53,3%) NN. La erradicación microbiológica se consiguió en 32 pacient es (59,3%), con la dist ribución: 8 (47,1%) con CL i.v., 15 (83,3%) con CL nebulizadas y 9 pacient es (69,2%) con la combinación CL i.v. más nebulizada. La curación clínica se
consigue en 42 pacient es (77,8%): 12 (80%) con CL i.v., 18 (94,7%) con CL nebulizada y 12 (85,7%)
con la combinación de CL nebulizada e int ravenosa. Est as diferencias no fueron significat ivas.
En el grupo de pacient es con infección por TB y NN (31 pacient es, 57,4%) la erradicación microbiológica se consiguió en 5 pacient es (100%) t rat ados con CL nebulizada y en 6 de 14 (42,9%)
t rat ados con CL i.v.; est a diferencia fue significat iva (p < 0,05). La curación clínica en est e grupo
fue del 100%(6 pacient es) t rat ados con CL nebulizada y del 75%(9 de 12) en el grupo de CL i.v.
Est a diferencia no fue significat iva.
Concl usiones: Nuest ro est udio señala que el t rat amient o con colist ina en pacient es con infección pulmonar por A. baumannii mult irresist ent e podría ser más eficaz si se administ ra nebulizada o en combinación con colist ina i.v. que si se administ ra de forma int ravenosa solament e..
© 2010 Elsevier España, S.L. y SEMICYUC. Todos los derechos reservados.
Introduction
Nosocomi al col oni zat i on and i nf ect i on caused by
mult iresist ant gramnegat ive bacilli have increased great ly
in recent years, and represent one of t he most serious
complicat ions in pat ient s admit t ed t o t he Int ensive Care
Unit (ICU). Among t he different mult iresist ant gramnegat ive
mi cr oor gani sms, Speci al ment i on must be made of
Acinet obact er baumannii. 1
The ant ibiot ic colist in was widely used bet ween t he 1960s
and 1980s due t o it s pot ent bact ericidal act ion, low incidence
of resist ances, and excellent act ivit y against gramnegat ive
baci l l i , i ncl udi ng mul t i r esi st ant st r ai ns. However, t he
associ at ed t oxi ci t y (nephrot oxi ci t y and neurot oxi ci t y)
event ually caused use of t he drug t o be abandoned. 2 In t he
1980s, colist in began t o be used via t he nebulized rout e in
pat i ent s wi t h cyst i c f i br osi s chr oni cal l y i nf ect ed wi t h
Pseudomonas aeruginosa. 3 On t he ot her hand, t he emergence
of inf ect ions due t o A. baumanni i in crit ical pat ient s has
ret urned t his ant ibiot ic t o t he front line in clinical pract ice.
There is evidence t hat nebulized colist in in conj unct ion
wit h t he int ravenous rout e could be useful for t he t reat ment
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228
of A. baumannii and P. aeruginosa infect ions. 4 The present
st udy describes our experience wit h t he use of nebulized
colist in f or t he t reat ment of respirat ory colonizat ion and
inf ect ion caused by A. baumannii in crit ical pat ient s. The
aim is t o evaluat e t he ef f icacy of nebulized colist in in t he
clinical eradicat ion and/ or clinical improvement (in t he
cont ext of t racheobronchit is and/ or nosocomial pneumonia)
of pat i ent s wi t h A. baumanni i i sol at ed f r om ai r way
cult ures.
M.J. Pérez-Pedrero et al
The pat i ent s w er e eval uat ed f or mi cr obi ol ogi cal
eradicat ion and clinical recovery. The lat t er was defined by
disappearance of t he fever, normalizat ion of t he leukocyt e
count s, disappearance or signif icant improvement of t he
r adi ol ogi cal i nf i l t r at es i n t he case of pneumoni a, and
disappearance or significant improvement of t he bronchial
secret ions in t he case of t racheobronchit is. Microbiological
eradicat ion in t urn was def ined by negat ive conversion of
t he respirat ory sample cult ure in at least t wo consecut ive
cult ures. Vigilance cult ures were conduct ed on a weekly
basis.
Material and method
A r et r ospect i ve st udy was made i n t he Depar t ment of
Int ensive Care Medicine of Virgen de la Salud Hospit al in
Toledo (Spain). We included all pat ient s wit h A. baumannii
posit ive airway sample cult ures (t racheobronchial aspirat e)
at any t ime during admission, and who received t reat ment
wit h colist in. All pat ient s were subj ect ed t o mechanical
vent ilat ion, t hough at t he t ime of t he diagnosis some of
t hem had al r eady been weaned f r om t he vent i l at or
(11 pat ient s; 20.4%) – wit h t racheot omy in all cases.
Col i st i n was admi ni st ered vi a t he i nt ravenous rout e,
nebulized, or via bot h rout es simult aneously (mixed). The
int ravenous dose was adj ust ed according t o renal funct ion.
The clinician in t urn decided t he dose of nebulized colist in,
using t hree regimens: 106 IU/ 8 h, 5 x 105 IU/ 6 h and 106
IU/ 12 h. The pat i ent s were di vi ded i nt o t hree cl i ni cal
groups:
– Nosocomial pneumonia (NP): diagnosis 48 hours af t er
admi ssi on, based on t he f ol l ow i ng cr i t er i a: new
radiological infilt rat es or progression of already exist ing
inf il t rat es, f ever > 38ºC wit hout any ot her expl aining
cause, l eukocyt osi s ( ≥ 12, 000/ μl ) or l eukopeni a
(< 4000/ μl ), purul ent sput um or i ncreased bronchi al
secret ion. Microbiological conf irmat ion of t he diagnosis
was made based on posit ive respirat ory sample cult ures
(bronchial aspirat e) wit h a signif icant bact erial count
(≥ 100,000 cfu/ ml).
– Tracheobronchit is (TB): f ever > 38ºC wit hout any ot her
explaining cause, leukocyt osis (≥ 12,000/ μl) or leukopenia
(< 4000/ μl) and purulent sput um or increased bronchial
secret ion wit hout radiol ogical inf il t rat es indicat ive of
pneumonia. Microbiological confirmat ion of t he diagnosis
was made based on posit ive respirat ory sample cult ures
(bronchial aspirat e)(≥ 100,000 cfu/ ml).
– Colonizat ion: posit ive cult ure in t he absence of crit eria of
infect ion.
Colonized pat ient s are not usually t reat ed wit h ant ibiot ics.
The i ncl uded col oni zed i ndi vi dual s were of t wo ki nds:
pat i ent s di agnosed wi t h i nf ect i on (and t he deci si on t o
provide t reat ment t herefore had been t aken), and pat ient s
who upon review were regarded as being only colonized,
since t hey did not meet t he diagnost ic crit eria for pneumonia
or t racheobronchit is. On t he ot her hand, we included some
colonized pat ient s t reat ed according t o t he crit erion of t he
supervising physician, on t he grounds t hat t he t reat ment of
colonizat ion by mult iresist ant microorganisms is warrant ed
i n cert ai n ci rcumst ances (e. g. , i n pat i ent s wi t h cyst i c
fibrosis colonized by Pseudomonas). 3
Statistical analysis
Qual i t at i ve vari abl es are present ed as absol ut e val ues
(percent ages), while quant it at ive variables are report ed as
t he mean ± st andard deviat ion (SD). The comparison of
cat egorical variables was based on t he chi-squared t est ,
wit h t he Fisher exact t est in 2 x 2 groups. The comparison of
quant it at ive variables in t urn was carried out wit h t he MannWhit ney U-t est . St at ist ical significance was considered for
p<0.05. The SPSS version 15.0 st at ist ical package was used
t hroughout (SPSS Inc., Chicago, IL, USA).
Results
We reviewed a t ot al of 83 pat ient s wit h posit ive cult ures for
col ist in-sensit ive A. baumanni i in bronchial secret ions.
Pat ient s considered by t he clinician t o be colonized and who
t herefore received no ant ibiot ic t reat ment were excluded.
A t ot al of 54 subj ect s were t reat ed wit h colist in and included
in t he st udy. Their baseline charact erist ics, including t he
severit y and mult iorgan dysf unct ion scores at t he t ime of
t he diagnosis of colonizat ion or inf ect ion, are report ed in
Tabl e 1. The most f requent causes of admi ssi on were:
polyt raumat ism, 17 pat ient s (31. 5%); st roke, 10 pat ient s
(18.6%); sept ic shock, 10 pat ient s (18.5%) and pneumonia,
8 pat ient s (14.9%).
A t ot al of 42. 6% of t he pat ient s were col onized by A.
baumanni i ; 29. 6% present ed t racheobronchit is and 27. 8%
pneumonia at t ribut able t o t his organism. In 35. 2% of t he
cases A. baumanni i was t he only microorganism isolat ed
from t he respirat ory t ract . The most frequent ly associat ed
microorganisms were: Klebsiella (2), E. coli (1), E. f aecium
(1) and Pseudomonas [1]. In 46.3%of t he cases colist in was
admi ni st er ed as onl y ant i bi ot i c – t he most f r equent l y
associat ed ant ibiot ic drugs being meropenem (7 cases),
aminoglycosides (6 cases), linezolid (4 cases), cefot axime /
cef t r i axone (3 cases), and pi per aci l l i n / t azobact am
(3 cases).
The nebulized colist in dose was 106 IU/ 8 h in 33.3%of t he
cases, 5 x 105 IU/ 6 h in 14.8%, and 106 IU/ 12 h in 14.8%. No
pat i ent devel oped er yt hema. In 14. 8% of t he pat i ent s
cort icost eroid premedicat ion was provided, and in no case
did bronchospasm occur when colist in was used in nebulized
f or m. Four pat i ent s ( 7%) devel oped nephr ot oxi ci t y
at t ribut able t o colist in. Table 1 also report s t he dif f erent
variables according t o t he t ype of colist in administ ered t o
t he pat ient .
Microbiological eradicat ion was achieved in 32 pat ient s
(59.3%). Specifically, eradicat ion was achieved in 47%of t he
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Nebulized colist in t reat ment of mult i-resist ant Acinet obact er baumannii pulmonary infect ion in crit ical ill pat ient s
229
Table 1 General charact erist ics of t he pat ient s and dist ribut ion of t he variables according t o t he t ype of colist in
administ ered
Tot al (n = 54)
Int ravenous colist in
(n = 18)
Nebulized colist in
(n = 21)
Mixed colist in
(n = 15)
Males
Age (years)
APACHE II
SOFA
Mechanical vent ilat ion
43 (79.6%)
57.1 ± 17.6
12.6 ± 5.3
4.4 ± 2.2
43 (79.6%)
15 (83.3%)
60.1 ± 17.4
12.8 ± 5.7
4.6 ± 2
15 (83.3%)
16 (76.2%)
55.5 ± 19.8
11.2 ± 4.3
3.7 ± 2
14 (66.7%)
12 (80%)
55.6 ± 14.8
14.1 ± 5.7
4.9 ± 2.4
14 (93.3%)
Clinical diagnosisa,b
Colonizat ion
Tracheobronchit is
NP
23 (42.6%)
16 (29.6%)
15 (27.8%)
4 (22.2%)
7 (38.9%)
7 (38.9%)
14 (66.7%)
7 (33.3%)
0
5 (33.3%)
2 (13.3%)
8 (53.3%)
St ay in ICU (days)
Hospit al st ay (days)
Nephrot oxicit y
Microbiological eradicat ion
Clinical recovery
Deat h
46.8 ± 34.3
66.1 ± 54.1
4 (7.4%)
32 (59.3%)
42 (77.8%)
12 (22.2%)
45.5 ± 36.5
64.1 ± 63
2 (11.1%)
8 (47.1%)
12 (66.6%)
5 (27.8%)
49 ± 40.2
70.9 ± 59
1 (4.8%)
15 (83.3%)
18 (85.7%)
4 (19%)
45.3 ± 22.7
61.9 ± 35
1 (6.7%)
9 (69.2%)
12 (80%)
2 (20%)
NP: nosocomial pneumonia.
a
In relat ion t o A. Baumannii.
b
p < 0.05 among t he t hree colist in administ rat ion groups.
pat ient s t reat ed wit h int ravenous colist in and in 83. 3% of
t hose t reat ed wit h nebulized colist in only. The dif f erence
bet ween t hese t wo groups was signif icant (p < 0. 05). On
analyzing the colonization group (23 patients), microbiological
eradicat ion was achieved in 76.9% of t he pat ient s t reat ed
wit h nebulized colist in, in 75%of t hose administ ered mixed
colist in, and in 66.7%of t he pat ient s t reat ed wit h int ravenous
colist in – t he differences in t his case being nonsignificant . In
t he pat i ent s wi t h t r acheobr onchi t i s and pneumoni a
(31 pat ient s), microbiological eradicat ion was achieved in
100%of t he pat ient s administ ered nebulized colist in, in 66.7%
of t hose administ ered mixed colist in, and in 42. 9% of t he
pat ient s t reat ed wit h int ravenous colist in. In t his case t he
difference bet ween nebulized and int ravenous colist in proved
significant (p < 0.05) (Fig. 1).
Clinical recovery was evident ly analyzed only in t he group
w i t h r espi r at or y i nf ect i on ( t r acheobr onchi t i s and
pneumonia), and occurred in 24 pat ient s (85.7%of t he t ot al
pat ient s st udied). Clinical recovery occurred in 100%of t he
6 pat ient s t reat ed wit h nebulized colist in only (all diagnosed
wit h t racheobronchit is), in 90%of t hose t reat ed wit h mixed
colist in, and in 75%of t hose t reat ed wit h int ravenous colist in
– no st at ist ical l y signif icant dif f erences being observed
among t hese groups.
growing emergence of mult iresist ant microorganisms such
as A. baumannii and P. aeruginosa complicat es t he t reat ment
of pat i ent s wi t h i nf ect i ons associ at ed t o mechani cal
vent ilat ion (pneumonia and t racheobronchit is), and has led
t o a change in t he approach t o t reat ment and t he ut ilizat ion
of ant ibiot ics such as colist in. The guides of t he American
Thoracic Societ y (ATS) indicat e t hat ant ibiot ics in aerosol
can be used f or t he t reat ment of i nf ect i ons caused by
m i c r oor gani sm s w i t h a h i gh m i n i m u m i n h i b i t or y
concent rat ion (MIC) and which are resist ant t o syst emic
t reat ment s. 5
100%
100%
100
90
76.9%
76,9%
80
70
66,7%
66.7%
66.7%
66,7%
66.7%
66,7%
60
50
42.9%
42,9%
40
COLISTINA
Intravenous
Intravenosa
Nebulizada
Nebulized
Mixta
Mixed
30
20
10
Discussion
Of t he different nosocomial infect ions seen in t he Int ensive
Care Unit , special ment ion must be made of respirat ory
infect ions in pat ient s subj ect ed t o mechanical vent ilat ion,
in view of t heir import ant frequency and repercussions. The
0
COLONIZATION
COLONIZACIÓN
(ENS)
(ENS)
INFECTION
INFECCIÓN
(p<0.05)
(P
< 0,05)
Fi gur e 1 Mi cr obi ol ogi cal er adi cat i on. Per cent age of
eradications in colonized and infected patients (tracheobronchitis
and nosocomial pneumonia).
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230
Colist in (polymyxin B) is an ant ibiot ic of great bact ericidal
capaci t y w i t h concent r at i on- dependent act i vi t y i n
applicat ion t o gramnegat ive bacilli, including mult iresist ant
st rains. Following it s discovery in t he 1940s, colist in use
peaked i n t he 1960s, f ol l owed by abandonment of i t s
administ rat ion due t o t he associat ed neurot oxicit y and
nephrot oxicit y. In t he 1980s t he drug was reint roduced in
nebulized f orm f or t he t reat ment of pat ient s wit h cyst ic
f ibrosis col onized by P. aer ugi nosa, in view of t he good
result s obt ained in t hese cases. 3,4 The aerosol administ rat ion
of ant ibiot ics is now being seen as a benef icial f orm of
t reat ment in pat ient s wit h respirat ory inf ect ion. 6 This is
mainly due t o t he high drug concent rat ions reached in t he
respirat ory t ract . In effect , t he administ rat ion of t wo million
nebulized unit s reaches peak sput um concent rat ion wit hin
one hour – t his being over 10 t imes higher t han t he MIC of
P. aer ugi nosa and A. baumanni i . Post er i or l y, t he
concent rat ion decreases, but maint ains an average of 4 μg/
ml 12 hour s af t er admi ni st r at i on, wi t h l ow syst emi c
concent r at i ons. 3 In t hi s w ay, nebul i zed or aer osol
administ rat ion would allow a reduct ion of t he drug doses
used in int ravenous ant ibiot herapy, by deposit ing t he drug
direct ly in t he sit e of infect ion. The blood concent rat ions in
t urn would be reduced, t oget her wit h t he t oxic side effect s
of colist in. 7 At present , when using t he nebulized rout e, t he
r ecommended dose i s 500, 000 uni t s/ 12 h f or pat i ent s
weighing under 40 kg, and one million unit s/ 8-12 h for t hose
weighing over 80 kg. In t he case of recurrent infect ions, t he
recommendat ion would be t wo million unit s every 8 hours. 8,9
The main inconvenience of t he aerosol f ormulat ion is t he
p ot ent i al i nd uct i on of l ocal si d e ef f ect s such as
bronchoconst rict ion. 6
In Oct ober 2009, Qin Lu et al. published an experiment al
st udy in pigs involving t he induct ion of vent ilat or-associat ed
pneumoni a due t o P. aer ugi nosa wi t h a MIC f or col i st i n
< 2 μg/ ml. 10 The animals were t reat ed wit h nebulized or
int ravenous colist in, and were sacrificed 48 hours aft er t he
t reat ment . In t he aerosol group t he mean peak concent rat ion
i n l ung t i ssue was 2. 8 μg/ g. In t he pi gs t r eat ed wi t h
int ravenous col ist in, t he col ist in concent rat ions in l ung
t i ssue were undet ect abl e. The aut hors concl uded t hat
nebulized colist in of f ers rapid and ef f ect ive bact ericidal
act ion, and proposed t he conduct ion of st udies warrant ing
it s use in pat ient s wit h pneumonia, as well as it s combinat ion
wit h t he int ravenous rout e in pat ient s wit h bact eremic
pneumonia. These dat a had been correlat ed t o clinical dat a
from previous years.
In t hi s cont ext , i n 2005, Kw a et al . publ i shed a
ret rospect ive st udy involving 21 pat ient s wit h pneumonia
due t o A. baumannii and P. aeruginosa. They reviewed t he
pat ient s t reat ed wit h nebul ized col ist in and recorded a
microbiol ogical eradicat ion rat e of 85. 7% and a cl inical
r ecover y r at e of 57. 1%. 11 In 2007, Per ei r a et al . used
inhalat ory colist in in 14 pat ient s wit h pneumonia in which
previous t reat ment wit h int ravenous colist in had failed, and
in anot her 5 pat ient s diagnosed wit h t racheobronchit is12 –
all of t hem wit h colist in-sensit ive gramnegat ive bacilli. The
pat i ent s wi t h pneumoni a wer e j oi nt l y t r eat ed wi t h
int ravenous and nebulized colist in, while t he pat ient s wit h
t racheobronchit is received only nebulized colist in; 93% of
t he pneumonias met crit eria of clinical recovery at t he end
of t reat ment , and 100% of t he cases of t racheobronchit is
M.J. Pérez-Pedrero et al
were healed. In 2008, Michalopoulos et al. used nebulized
col i st i n t o t r eat 60 cr i t i cal pat i ent s di agnosed wi t h
pneumoni a caused by A. baumanni i , P. aer ugi nosa and
Kl ebsi el l a pneumoni ae; 57 of t he pat ient s also received
syst emic t reat ment . 13 The aut hors observed clinical recovery
and microbiological eradicat ion in 83.3%of t he cases, and
concluded t hat nebulized colist in can be regarded as an
adj uvant t o i nt ravenous admi ni st rat i on i n pneumoni as
caused by col i st i n-sensi t i ve mi croorgani sms i n cri t i cal
pat ient s. Likewise in 2008, Fagalas et al. published a series
of 5 pat i ent s w i t h nosocomi al pneumoni a due t o
A. baumannii and P. aeruginosa t reat ed only wit h nebulized
colist in and wit hout adj unct ive int ravenous t herapy. Four of
t he 5 pat ient s (80%) recovered and survived. 14 The aut hors
concluded t hat t reat ment wit h nebulized colist in alone in
applicat ion t o pneumonias caused by microorganisms t hat
are sensit ive t o t his drug deserves t o be st udied more in
dept h. In 2009, Korbila et al. published a ret rospect ive st udy
of 78 pat ient s wit h vent ilat or-associat ed pneumonia t reat ed
wit h int ravenous plus nebulized colist in, versus 43 pat ient s
t reat ed wit h t he int ravenous f ormulat ion only. 15 Clinical
recovery was recorded in 79.5%of t he pat ient s in t he first
group and in 60.5%of t he pat ient s t reat ed wit h int ravenous
colist in only – t he dif f erence being st at ist ically signif icant
(p < 0.025).
Our study shows colistin in mixed administration (nebulized
and intravenous) to be superior for the treatment of respiratory
infect ion due t o A. baumannii t han int ravenous t reat ment
only. The use of nebulized colist in, alone or in combinat ion,
improved t he result s in t erms of microbiological eradicat ion
and clinical recovery in all the treatment groups.
Our st udy has clear limit at ions, including it s ret rospect ive
nat ure and t he limit ed number of pat ient s in each group.
Anot her limit at ion is t he use of different dosing regimens.
The regimen was decided by t he physician t reat ing t he
pat ient , and was independent of t he nosologic charact erist ics
of t he case (colonizat ion, t racheobronchit is or pneumonia).
The exist ing lit erat ure describes different dosing regimens,
t hough none have been shown t o be superior t o t he rest .
Nevert heless, we feel t he regimen used t o be represent at ive
of our cl inical experience in t he dail y use of nebul ized
colist in in pat ient s of t his kind. 16
Special ment ion should be made of t he group of pat ient s
wit h t racheobronchit is t reat ed wit h nebulized colist in only.
The 5 pat ient s recovered, and microbiological eradicat ion
was achieved in all of t hem, while in cont rast in t he group
of subj ect s t reat ed via t he int ravenous rout e, only t hree out
of 5 r ecover ed (60%). These dat a ar e not st at i st i cal l y
signif icant , due t o t he small number of pat ient s involved,
t hough despit e t he l imit at ions of our st udy, t he resul t s
suggest t hat nebulized colist in alone should be viewed as an
alt ernat ive for t he t reat ment of t hese pat ient s.
In our series, t he pat ient s t reat ed wit h nebulized colist in
achieved a significant ly higher microbiological eradicat ion
rat e t han t he group subj ect ed t o int ravenous t reat ment .
The cases diagnosed wit h pneumonia also achieved bet t er
result s wit h combinat ion t reat ment t han wit h int ravenous
dosing alone. The infect ed pat ient s who all recovered (100%)
wit h nebulized colist in all present ed t racheobronchit is; no
pat i ent di agnosed wi t h pneumoni a was t r eat ed wi t h
nebul i zed col i st i n onl y. On j oi nt l y consi der i ng al l t he
pat i ent s wi t h i nf ect i on, i . e. , t r acheobr onchi t i s and
Documento descargado de http://www.medintensiva.org el 17/11/2016. Copia para uso personal, se prohíbe la transmisión de este documento por cualquier medio o formato.
Nebulized colist in t reat ment of mult i-resist ant Acinet obact er baumannii pulmonary infect ion in crit ical ill pat ient s
pneumoni a, t he mi cr obi ol ogi cal er adi cat i on r at e was
likewise significant ly favorable t o t he group wit h nebulized
colist in versus t hose administ ered int ravenous colist in only.
In conclusion, our dat a coincide wit h t hose f ound in t he
lit erat ure: t reat ment wit h inhalat ory colist in improves t he
result s in pat ient s wit h respirat ory infect ions produced by
A. baumannii. Despit e t he limit at ions of our st udy, we feel
t hat inhalat ory colist in should be regarded as an adj unct t o
int ravenous dosing of t he drug in pat ient s wit h nosocomial
pneumonia due t o A. baumannii. Colist in administ rat ion in
nebulized form only, wit hout associat ed int ravenous t herapy,
could be an alt ernat ive in pat ient s wit h t racheobronchit is,
or might possibly be t he t reat ment of choice f or securing
microbiological eradicat ion in colonized pat ient s.
Conflict of interest
6.
7.
8.
9.
10.
11.
The aut hors declare no conflict of int erest .
12.
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