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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- 1. Grothe C, Silva Belasco AG, de Cássia Bittencourt AR, Vianna LA, de Castro Cintra Sesso R, Barbosa DA. Incidence of blood stream infection among patients on hemodialysis by central venous catheter. Rev. Further studies are suggested that correlate Latinoam Enfermagem. 2010;18(1):73-80.
cross-infection to be harnessed to analyze the 2. Saxena AK, Panhotra BR. Haemodialysis catheter-related bloodstream colonization of patients with chronic renal fail- infections: current treatment options and strategies for prevention. Swiss Med Wkly. 2005;135(9-10):127-38. Review.
ure before starting dialysis therapy, thereby en- 3. Grayson ML. The treatment triangle for staphylococcal infections. N abling the evaluation of the issues involved in cross-transmission of microorganisms and the 4. Deshpande LM, Fritsche TR, Moet GJ, Biedenbach DJ, Jones RN. development of ICS, preventing the emergence Antimicrobial resistance and molecular epidemiology of vancomycin- of these pathogens, thus reducing the high le- resistant enterococci from North America and Europe: a report from the SENTRY antimicrobial surveillance program. Diagn Microbiol Infect 5. Fram D, Castrucci FM, Taminato M, Godoy-Martinez P, Freitas MC, Belasco A, Sesso R, Pacheco-Silva A, Pignatari AC, Barbosa D. Cross-transmission of vancomycin-resistant Enterococcus in patients undergoing dialysis and kidney transplant. Braz J Med Biol Res. Among the main microorganisms isolated in 6 Centers for Disease Control and Prevention. Guidelines for the cultures of hemodialysis patients by central ve- Prevention of Intravascular Catheter-Related Infections – 2011 [Internet]. [cited 2013 Apr 6]. Available from: http://www.iagsaude.
nous catheter, the S. aureus were predominant com.br/cdc-centers-for-disease-control-and-prevention-diretrizes- in the three collection locations. We found that para-a-prevencao-de-infeccao relacionada-ao-cateter-vascular-2011/ in the catheters implanted and maintained for 7. Grundmann H, Aanensen DM, van den Wijngaard CC, Spratt BG, Harmsen D, Friedrich AW; European Staphylococcal Reference a period exceeding 21 days, there were signifi- Laboratory Working Group. Geographic distribution of Staphylococcus cant increases in the number of microorganisms aureus causing invasive infections in Europe: a molecular- isolated, with an increase of resistant strains of epidemiological analysis. PLoS Med. 2010 Jan 12;7(1):e1000215.
virtually all microorganisms. We observed an el- 8. Ofner-Agostini A, Varia M, Johnston L, Green K, Simor A, Amihod B, Bryce E, Henderson E, Stegenga J, Bergeron F, Canadian Nosocomial evated resistance exceeding 70%, of the micro- Infection Surveillance Program, Gravel D. Infection control and organisms to the antibiotics tested. Patients who antimicrobial restriction practices for antimicrobial resistant organisms (aros) in canadian tertiary care hospitals. Am J Infect Control. presented resistant strains had a 50% increased risk of death compared to the other microorgan- 9. National Kidney Foundation. K/DOQI Clinical practice guidelines for isms. The observed mortality was 100% in the vascular access and Clinical Practice Recommendations.Prevention group of patients with endocarditis due to meth- and treatment of catheter and port complications guideline 7. New York; 2006. {Internet]. [cited 2013 Abr 6]. Available from: http://www.
icillin-resistant Staphylococcus aureus (MRSA).
kidney.org/professionals/KDOQI/guideline_upHD_PD_VA/va_guide7.
Collaborations
10. Clinical and Laboratory Standards Institute.CLSI. Performance standards for antimicrobial susceptibility testing. 20th. USA: Suppl Esmanhoto CG participated in the project de- sign, planning, interpretation of data, drafting 11. Rice LB. Antimicrobial resistance in gram-positive bacteria. Am J Infect of the article and critical revision of the content. Control. 2006;34(5 Suppl 1):S11-9; discussion S64-73. Review.
Taminato M and Fram DS contributed in the de- 12. León C, Ariza J; SEIMC; SEMICYUC. [Guidelines for the treatment of sign and planning steps the project. Belasco AGS short-term intravascular catheter-related infections in adults; SEIMC- SEMICYUC Consensus Conference]. Enferm Infecc Microbiol Clin. contributed in data interpretation and critical 2004 Feb;22(2):92-101. Review. Spanish.
review of the content. Barbosa DA collaborated 13. United States Renal Data System [homepage on the Internet]. with the project design, planning, interpretation Bethesda: National Institutes of Health, National Institute of Diabetes of data, drafting the article, critical revision of and Digestive and Kidney Diseases; c2007 [updated 2007]. Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal the content and final approval of the version to Disease in the United States; Chapter 2: ESRD incidence & prevalence [Internet]. [cited 2013 Apr 5]. Available from: http://www.usrds.
Acta Paul Enferm. 2013; 26(5):413-20.
Microorganisms isolated from patients on hemodialysis by central venous catheter and related clinical evolution Control Hosp Epidemiol. 2006;27(11):1233-41.
14. Galoisy-Guibal L, Soubirou JL, Desjeux G, Dusseau JY, Eve O, 15. Arduíno MJ, Tokars JI. Why is an infection control program Escarment J, Ecochard R. Screening for multidrug-resistant bacteria needed in the hemodialysis setting? Nephrol News Issues. as a predictive test for subsequent onset of nosocomial infection. Infect Acta Paul Enferm. 2013; 26(5):413-20.

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