Original Article
Microrganismos isolados de pacientes em hemodiálise por
cateter venoso central e evolução clínica relacionada
Keywords Abstract
Nursing care; Clinical nursing research;
Objective: To identify the microorganisms isolated on the pericatheter skin, catheter tip and blood stream of
patients on hemodialysis by central venous catheter, to verify the profile of sensitivity of these microorganisms
to antimicrobials and to assess the clinical evolution and mortality related to these microorganisms.
Methods: A cross sectional study. The strains were isolated from the patients on hemodialysis by central venous catheter that, in a previous study, presented pericatheter skin, catheter tip and blood stream infection
Descritores
and were analyzed for microbiological profile and lethality related.
Results: 128 microorganisms were isolated in the bloodstream in the 94 patients studied. There were 35
cases of septicemia and 27 of endocarditis. The mortality in cases of endocarditis due to methicillin-resistant
Staphylococcus aureus was 100%.
Conclusion: Infection in the bloodstream and endocarditis caused by methicillin-resistant Staphylococcus aureus was predictive of mortality and lethality. Submitted
Objetivo: Identificar os microrganismos isolados da pele pericateter, ponta do cateter e corrente sanguínea de
pacientes em hemodiálise por cateter venoso central, verificar o perfil de sensibilidade destes microrganismos
Accepted
aos antimicrobianos e avaliar a evolução clínica e a mortalidade relacionada a estes microrganismos.
Métodos: Estudo transversal. As cepas isoladas de pacientes em hemodiálise por cateter venoso central que em estudo prévio apresentaram infecção na pele pericateter, ponta do cateter e corrente sanguínea foram analisadas quanto ao perfil microbiológico e letalidade relacionada. Resultados: Foram isolados 128 microrganismos em corrente sanguínea nos 94 pacientes estudados. Ocorreram 35 casos de septicemia e 27 de endocardite. A letalidade nos casos de endocardite por Staphylococcus aureus resistente à meticilina foi 100%. Conclusão: Infecção em corrente sanguínea e endocardite por Staphylococcus aureus resistente à meticilina são preditivas de alta mortalidade e letalidade.
Corresponding author Cibele Grothe Esmanhoto Napoleão de Barros street, 754, Vila Clementino, São Paulo, SP, Brazil. Zip Code: 04024-002
1Escola Paulista de Enfermagem, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
Conflicts of interest: there are no conflicts of interest to report.
Acta Paul Enferm. 2013; 26(5):413-20.
Microorganisms isolated from patients on hemodialysis by central venous catheter and related clinical evolution
At the end of 1986, in Europe, and 1988, in
the United States, clinically significant resistance to
Infection is a frequent cause of rehospitalization
vancomycin was identified among the enterococci.
and the second leading cause of death in chronic
At this time, infections caused by coagulase-nega-
renal patients on hemodialysis. The central venous
tive Staphylococcus with reduced susceptibility to
catheter is largely responsible in the majority of cas-
es.(1) Studies have focused primarily on the patient’s
The emergence of resistance among the S. au-
skin around the insertion site, followed by the the
reus to the glycopeptides became a constant concern
colonization of the catheter insertion site, coloniza-
among researchers. The transfer of the vanA gene
tion of the catheter by hematogenous dissemination
of the enterococci for S. aureus at the experimen-
from elsewhere and/or contamination of the infu-
tal level suggested the potential of staphylococci
sion liquid. In addition, dialysis patients are known
to acquire these genes in vivo, producing clinical
to suffer from weakened defense mechanisms, at-
resistance.(7) Data from the Canadian Nosocomial
tributed in large proportions to the elevated comor-
Infection Surveillance Program showed that for ev-
bidity of diabetes mellitus and malignancies, as well
ery thousand hospitalizations in 2007, there were
as malnutrition particularly associated with uremia
8.62 new patients infected by MRSA and 1.32 new
patients with S. aureus resistant to vancomycin per
Among the microorganisms, bacteria contribute
to approximately 95% of infections, with a consid-
As a function of high morbidity and mortality
erable percentage of bacterial isolates resistant to
related to the infectious complications in hemo-
antimicrobials. Antimicrobial resistance is a global
dialysis patients, we were motivated to conduct
and growing concern. The transfer of resistant mi-
this study, which had as its objectives: to identify
croorganisms among patients, possibly, occurs via
the primary microorganisms isolated on the peri-
the hands and/or the respiratory tract of the health
catheter skin, at the tip of the catheter, and in the
professionals, which can be contaminated at the
bloodstream of patients undergoing hemodialysis
time of contact with the patient and surfaces.(3)
treatment by central venous catheter; to trace the
From the epidemiological point of view, the
profile of sensitivity of these microorganisms to
Gram-positive cocci have emerged as key players,
antimicrobials; and, to assess the clinical evolution
especially Staphylococcus aureus, coagulase-negative
and case fatality related to these microorganisms in
staphylococci and enterococci.(3,4,5) Although coag-
ulase-negative staphylococci are frequently isolated
in blood cultures, they are clinically significant in
less than 15.0% of cases. By being part of the skin
microbia and submitting a relatively low virulence,
they are usually considered contaminants of blood
This was a cross-sectional study conducted in the
cultures. Although the bacteremia by Gram-nega-
University Hospital of the Federal University of São
tive rods have become less frequent, the associated
Paulo, in the southeastern region of Brazil, in the
mortality is higher when compared to Gram-posi-
Records from 156 patient charts in hemodialy-
The prevalence of methicillin-resistant Staphylococ-
sis who used central venous catheters as the access
cus aureus (MRSA) has increased dramatically, becom-
route were studied, document analysis was made of
ing responsible for more than half of staphylococcal
the isolated microorganisms, of the variables relat-
infections in various healthcare services worldwide.
ed to the length of time for catheter permanence,
According to the Centers for Disease Control and Pre-
and infectious complications of 94 patients who
vention, it is estimated that approximately 25-30% of
developed infections in the bloodstream, the peri-
the population is a carrier of the bacteria.(6)
catheter skin or catheter tip. The catheter removal
Acta Paul Enferm. 2013; 26(5):413-20.
Esmanhoto CG, Taminato M, Fram DS, Belasco AGS, Barbosa DA
occurred in the following situations: malfunction-
em, meropenen, netilmicin, nitrofurantoin, nor-
ing of the catheter, presence of local erythema and/
floxacin, oxycillin, teicoplanin, tobramycin, and
or purulent secretion or bacteremia without other
vancomycin) were placed in an oven at ± 35 º C for
identifiable source of infection as recommended by
24 hours for further reading of the halos. The in-
National Kidney Foundation Kidney Disease Out-
terpretation of the results was performed according
comes Quality Initiative (NKF KDOQI).(9)
to the criteria established by the CLSI M100-S20.
The pericatheter skin samples were obtained us-
Staphylococcus aureus ATCC 25923 E. faecalis
ing a swab - pre-moistened cotton swab - in a solu-
ATCC 29212, and Klebsiella pneumoniae carbap-
tion of calcium alginate (Diagnostic Cefar-Farmaco,
enemase-producing ATCC BAA-1705 strains were
São Paulo, Brazil), and were transported to the mi-
crobiology laboratory, where they were immediately
A descriptive analysis was performed, and pre-
rolled onto plates containing tryptic soy agar with
sented in absolute numbers and percentages. We
5% sheep’s blood and agar of mannitol-salt (Difco
calculated the odds ratios and confidence intervals
Laboratories, Detroit, MI). All cultures were incu-
(95% CIs). The statistical program used was the
bated at a temperature of 35° C for 48 hours, and
Statistical Package for the Social Sciences (SPSS),
examined daily to search for evidence of growth.
The blood samples (20 ml) of the patients
The study followed the development of national
were collected in Batec vials and the cultures were
and international standards of ethics in research in-
processed by means of an automated method for
isolating microorganisms (Bactec 9240, Becton
After removing the catheter, approximately 50
mm from its tip was rolled across the plates of Ro-
dac that contained tryptic soy agar with 5% sheep’s
In table 1, the 240 microorganisms are presented
blood (COMO, Oxoid, Basingstoke Hampshire,
that were isolated in the cultures of 94 patients in
United Kingdom), and mannitol salt agar (ASM,
hemodialysis through the central venous catheter
Oxoid), which were previously prepared in the lab-
oratory according to the semi-quantitative method.
The gram-positive microorganisms were pre-
Catheters that presented more than 15 colony form-
dominant and among these the S. aureus (76%) were
ing units were considered significantly colonized.
The disk diffusion method was employed to de-
termine the susceptibility profile, where the culture
plates of blood agar were selected for three to five
isolated and pure colonies, and further, transferred
to a tube containing 5 ml of saline solution. The
bacterial suspension had a measured turbidity in the
Shaplylococcus coagulase – negativo (18) 8(31)
digital turbidimeter (Baxter, Sacramento, USA) and
the scale used was a that of 0.5 McFarland, which
corresponds to a bacterial concentration of about 1
to 2 x 108 CFU/ml. The sowing was carried out on
a Müller-Hinton agar board, as recommended by
The plates containing the discs impregnated
with the clavulanic acid, and antibiotics (amika-
cin, cefepime, cefoxitin, ceftazidime, ciprofloxacin,
clindamycin, erythromycin, gentamicin, imipen-
Legend: Skin – n=54; Tip – n=58; Blood – n=128
Acta Paul Enferm. 2013; 26(5):413-20.
Microorganisms isolated from patients on hemodialysis by central venous catheter and related clinical evolution
isolated more frequently in the three sampling sites,
We found that in the catheters implanted and
with 51% of the isolates in the skin at the cathe-
maintained for a period exceeding 21 days, there
ter insertion site, 77% of the isolates at the catheter
were significant increases in the number of microor-
tips, and 85% of isolates in the blood. Among the
ganisms, and also an increase of resistant strains of
Gram-negative microorganisms, Pseudomonas aeru-
virtually all organisms, and that the resistant strains
ginosa (40%), and Acinetobacter baumannii (34%)
were 80% more isolated with the increased central
were prevalent, being the most frequently isolated
in the blood (43% -34%) in the catheter tip (39%
After 21 days of implantation of central ve-
-39%) and in the skin at the catheter insertion site
nous catheter, the risk of isolating strains of S. aureus was 50% higher compared to other micro-
The fungi were less prevalent (13%), and Can-
organisms, with strains of Staphylococcus aureus
dida spp appeared in 73% of these. Unlike the
resistant to methicillin being two times more iso-
gram-positive and gram-negative bacteria, fungi
lated than MSSA strains (Odds: 2.04, CI: 0.54 to
were isolated more frequently in the skin at the
7.70). Resistant strains of Pseudomonas aerugino-
catheter insertion site (31%), followed by the cath-
sa were isolated four times more (odds: 4.00, CI:
eter tip (8%) and less frequently in the blood (6%).
0.37 to 42.3) than the sensitive strains, and resis-
Table 2 shows the analysis of the profile of sen-
tant strains of Acinetobacter baumannii were three
sibility of the isolated microorganisms with higher
times more isolated than the susceptible strains
frequency in the blood cultures and the permanence
In table 3 we present the clinical evolution of
patients and the related lethality to the profile of the
Table 2. Profile of the sensiblity of the microorganisms and
microorganisms isolated in the blood stream.
permanence of the central venous catheter
Of the 94 patients previously studied, 62 (66%)
developed severe infectious complications, 35
(56%) sepsis, and 27 (44%) endocarditis. Of the
patients with endocarditis, 15 (56%) died.
Seventeen strains were isolated from blood cul-
tures of the 12 patients who developed septicemia
and died. It was found that strains of Staphylococ-cus aureus were the most prevalent, among which
36.5% were due to strains with 70% resistance to
five or more of the 11 antibiotics tested. The risk
of death was 50% higher in patients with resistant
strains, four times greater (odds: 4.3, CI: 0.80 to
22.90) in patients with septicemia who presented
Legend: TC – Time of catheter; *TC>21days – n=77; ** TC=<21days – n=22
strains of Staphylococcus aureus resistant to methicil-
lin, compared to other microorganisms.
We observed an elevated resistance higher
Sixteen strains were isolated from the blood cul-
than 70%, of the micro-organisms to the 11 an-
tures of the 15 patients who developed endocarditis
tibiotics tested, and the S. aureus was only 100%
and died. The Staphylococcus aureus were the most
sensitive to teicoplanin and vancomycin. Among
prevalent, among which 60% were of strains with
the non-fermenting gram-negative bacilli, P.
70% of resistance to five or more antibiotics of the
aeruginosa was 100% sensitive only to clavulanic
11 tested. The lethality observed the group of pa-
acid and tazobactam, and the A. Baumanii pre-
tients with endocarditis due to MRSA was 100%
sented a highly resistant profile, 80% sensitive
(odds: 11.0; IC :1,16-103, 94). We emphasize that
52% of the patients with a confirmed diagnosis of
Acta Paul Enferm. 2013; 26(5):413-20.
Esmanhoto CG, Taminato M, Fram DS, Belasco AGS, Barbosa DA
Table 3. Clinical evolution and lethality related to the profile of microorganisms isloated in the blood stream
Legend: Septicemia – n=35; *Death – n=12; Endocarditis – n=27; **Death – n=15
endocarditis presented concomitantly the same mi-
can also colonize the inner surface of the catheter,
croorganism isolated from the blood and the cath-
where they adhere and can become incorporated
into a biofilm which enables the sustenance of the
local infection and hematogenous dissemination.
When catheters are used for long periods, intralu-
minal colonization is greater than extraluminal.(2)
The contamination of the connection was the
The occurrence of infections caused by resistent mi-
possible origin of colonization in long-term indwell-
croorganisms constitutes a worldwide public health
ing catheters (greater than 30 days), responsible for
problem. Resistent bacterias, such as Acinetobacter
infection related to the central venous catheter,
baumannii, Staphylococcus aureus, Pseudomonas
while pericatheter skin contamination determined
aeruginosa, Klebsiella pneumoniae and Enterococcus
the beginning of colonization of the short-term
spp, have become increasingly common in health
catheter (less than 10 days).(12) Given these results,
researchers concluded that the permanence of the
The infections caused by gram-positive patho-
central venous catheter is considered a major cause
gens are still shown to be predominant, character-
of infection.(1,2,12) In the USA about five million
ized by a reduced sensitivity profile to different anti-
central venous catheters are introduced annually. In
microbials, which contributes to reducing the ther-
this context, data from the CDC indicate blood-
apeutic options and the high rates of mortality.(11)
stream infection rates related to the catheters of 5.3
The high rates of catheter-related blood stream
per 1000 catheter-days, with a rate of colonization
infection (CRBSI) associated with the increased
growth in the rates of resistence have made these in-
In the present study we found that in the cath-
fections particularly worrisome. Various conditions
eters implanted and maintained for a period ex-
have been identified as risk factors for the develop-
ceeding 21 days, there were significant increases in
ment of CRBSI, such as the duration of catheter
the number of microorganisms isolated, with an
placement, skin colonization at the catheter inser-
increase in resistant strains of virtually all microor-
tion site, and the frequent manipulation of the ve-
ganisms. After 21 days of implantation of the cen-
tral venous catheter, the risk of isolating strains of S.
The skin is the principal source for colonization
aureus increased by two times, methicillin resistant
and infection of the short-dwelling catheter. The
Staphylococcus aureus was isolated five times more
bacteria that are in the skin of the patient migrate
in catheters with a permanence time greater than
along the surface, colonizing the distal end, result-
21 days. The risk of isolating strains of Pseudomo-
ing in infection. However, these micro-organisms
nas aeruginosa and Acinetobacter baumannii after 21
Acta Paul Enferm. 2013; 26(5):413-20.
Microorganisms isolated from patients on hemodialysis by central venous catheter and related clinical evolution
days of implantation of the central venous catheter
of the vanA enterococci gene for S. aureus at the
doubled, and the multiresistant strains were 90%
experimental level suggested the potential of staph-
more isolated with increasing permanence of cen-
ylococci to acquire these genes in vivo, producing
clinical resistance. In addition, laboratory studies
The discovery of the antimicrobials revolu-
with coagulase-negative Staphylococcus and S. aureus
tionized the treatment of infections, but their in-
exposed to progressively higher levels of glycopep-
discriminate use has led to the rapid emergence
tides demonstrated the ability of these agents to se-
of bacterial resistance, which shows increasing
prevalence in healthcare facilities.(3) Currently,
In our study we observed an elevated resistance,
in the USA, 55% of infections caused by Staph-
greater than 70%, of the microorganisms to the antimi-
ylococcus aureus are related to MRSA. In France,
crobials tested, and S. aureus was only 100% sensitive
isolation of resistant bacteria ranges from 30%
to teicoplanin and vancomycin. Among the non-fer-
to 40%, reaching a percentage of up to 78% of
menting gram-negative bacilli, P. aeruginosa was 100%
sensitive only to the clavulanic acid and tazobactam
According to SENTRY (the Program of Anti-
and the A. Baumanii presented a highly resistant pro-
microbial Surveillance) results from Latin Amer-
file, 80% sensitive only to the Imipenem.
ica and Brazil, the non-fermenting Gram neg-
Patients hospitalized with infecction by S. au-
ative rods (Acinetobacter spp. and Pseudomonas reus have a five times higher risk of mortality.(13)
aeruginosa) multidrug-resistance, and the En-
Mortality associated with bacteremia, caused by S. terobacteriaceae (Escherichia coli, Salmonella spp,
aureus, varies from 11.9 to 46.5% per year.(15)
Shigella spp and Proteus mirabilis), producers of
the extended spectrum beta-lactamase (ESBL)
the Centers for Disease Control and Prevention
constitute the main problem in pharmaceutical
(CDC) are adopted in our service, the blood
resistence in these countries. We observed high
stream infection (BSI) mortality and the lethal-
rates of resistant isolates, except the polymyxins,
ity related to the use of central venous catheters
since the program’s inception, in 1997.(14) Of the
for dialysis is elevated, as well as the prevalence
Gram-positive cocci, oxycillin resistance among
of the resistant microorganisms. In this study,
staphylococci represents an important problem
62 patients developed severe infectious compli-
in Latin America and the United States. Howev-
cations, 37% with septicemia, 29% with endo-
er, rates vary significantly between hospitals and
carditis - 56% of these resulted in death. The
countries, although the percentage of isolates
risk of death was higher than 50% in patients
of Staphylococcus aureus sensitive to oxacillin
with resistant strains, four times higher in pa-
originatimg from cases of bacteremia in Brazil,
tients with septicemia who presented strains of
in comparison to Latin America, has been ap-
MRSA, compared to other microorganisms. The
proached: 68.2% and 68.5%, respectively.(14)
lethality rate was 100% in the group of patients
The prevalence of MRSA increased dramatical-
ly, becoming responsible for more than half of the
This study is in line with the current litera-
staphylococcal infections in various healthcare ser-
ture, complementing the results of the previously
vices worldwide. At the end of the 1980s, clinically
published studies in this journal, reinforcing that
significant resistance to vancomycin became iden-
S. aureus are responsible for most infections and
tified among enterococci (VRE). At this time, in-
that their control proposes a challenge. Since the
fections caused by coagulase-negative staphylococci
possibility of the emergence of bacteria resistant to
(CNS), with reduced susceptibility to vancomycin
all available antimicrobials in clinical practice is a
have also been described. The emergence of resis-
current reality, health professionals should be aware
tance among S. aureus to glycopeptides has become
of precautions, including staff education on prop-
a constant concern among researchers. The transfer
er techniques for insertion and maintenance of the
Acta Paul Enferm. 2013; 26(5):413-20.
Esmanhoto CG, Taminato M, Fram DS, Belasco AGS, Barbosa DA
central venous catheter and instituting more effec-
tive and efficient quality control measures, aimed
at reducing horizontal transmission of these patho-
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Superior Tribunal de Justiça EDcl no AgRg no RECURSO ESPECIAL Nº 255.170 - SP (2000/0036627-7) MINISTRO LUIZ FUX MINISTÉRIO PÚBLICO DO ESTADO DE SÃO PAULO EMBARGOS DECLARAÇÃO ACÓRDÃO PROFERIDO REGIMENTAL. AMBIENTAIS. AÇÃO CIVIL PÚBLICA. RESPONSABILIDADE. ADQUIRENTE. TERRAS RURAIS. RECOMPOSIÇÃO. MATAS. 1. A Medida Provisória 1.736-33 de 11/02/99,
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