Central venous catheter-related bloodstream infection caused by Staphylococcus aureus: microbiology and risk factors

Abstract

Although central vascular catheters (CVC) are indispensable in modern medicine, they are an important risk factor for primary bacteremias. We examined the incidence and risk factors associated with catheter-related bloodstream infection (CR-BSI) caused by Staphylococcus aureus in surgical patients. A prospective study was carried out in the Hospital das Clínicas da Universidade Federal de Uberlândia (HC-UFU) from September 2000 to December 2002. The skin insertion site, catheter tip, and blood were microbiologically analyzed. Demographics and risk factors were recorded for each patient, and cultures were identified phenotypically. Staphylococcus aureus was the most frequent pathogen, with an incidence rate of 4.9 episodes of CR-BSIs per 1,000 catheter/days. Based on logistic regression, the independent risk factors were: colonization on the insertion site =200 colony forming units (CFU)/20 cm² (p=0.03; odds ratio (OR) =6.89) and catheter tip (p=0.01; OR=7.95). The CR-BSI rate was high; it was mainly associated with S. aureus, and skin colonization at the insertion site and on the catheter tip were important risk factors for CR-BSI.

Staphylococcus aureus; ventral venous catheter; bloodstream infection

ORIGINAL PAPERS

Central venous catheter-related bloodstream infection caused by Staphylococcus aureus: microbiology and risk factors

Geraldo Sadoyma^I; Augusto Diogo Filho^II; Paulo Pinto Gontijo Filho^I,II

^ILaboratory of Microbiology

^IICCIH of Clinical Hospital of Federal University of Uberlândia; Uberlância MG, Brazil

^{Address for correspondence}

ABSTRACT

Although central vascular catheters (CVC) are indispensable in modern medicine, they are an important risk factor for primary bacteremias. We examined the incidence and risk factors associated with catheter-related bloodstream infection (CR-BSI) caused by Staphylococcus aureus in surgical patients. A prospective study was carried out in the Hospital das Clínicas da Universidade Federal de Uberlândia (HC-UFU) from September 2000 to December 2002. The skin insertion site, catheter tip, and blood were microbiologically analyzed. Demographics and risk factors were recorded for each patient, and cultures were identified phenotypically. Staphylococcus aureus was the most frequent pathogen, with an incidence rate of 4.9 episodes of CR-BSIs per 1,000 catheter/days. Based on logistic regression, the independent risk factors were: colonization on the insertion site =200 colony forming units (CFU)/20 cm² (p=0.03; odds ratio (OR) =6.89) and catheter tip (p=0.01; OR=7.95). The CR-BSI rate was high; it was mainly associated with S. aureus, and skin colonization at the insertion site and on the catheter tip were important risk factors for CR-BSI.

Key Words:Staphylococcus aureus, ventral venous catheter, bloodstream infection.

Safe vascular access is one of the key factors for modern medical practice; however, the intravascular devices (IVDs) needed for establishing reliable access are significantly associated with iatrogenic disease, especially bacteremia and candidemia [1,2]. Over 250,000 bloodstream infections (BSI) related to the presence of IVDs occur each year in the U.S., with an attributed death rate of 12-25%; BSIs also extend hospital internment, with additional costs of US$33,000-35,000/patient [3,4]. Among IVDs, the use of central venous catheters (CVCs) is frequently followed by both local and systemic complications, including septic thrombophlebitis, endocarditis, metastatic infections, and bacteremias [5].

It is estimated that over 80% of all catheter-related bloodstream infections (CR-BSIs) are associated with CVCs, although they account for only a small percentage of all vascular catheters. CR-BSIs cause substantial morbidity and mortality, and they increase internment time and costs [6].

The pathogenesis of CR-BSI is multifactorial and complex. Although venous and arterial catheters may be colonized via the bloodstream from infections at other sites, through intestinal translocation or through administration of fluids (intrinsic contamination), available data suggest that most infections by staphylococci result from the migration of these microorganisms from the skin insertion site or from the catheter hub [7].

According to the "US National Nosocomial Infections Surveillance System Report", the pathogens most frequently associated with CR-BSI etiology from 1991-1999 were: coagulase-negative Staphylococcus (CoNSs) (37%), S. aureus (13%), Enterococcus spp. (13%), and Candida albicans (8%)[8].

We evaluate the pathogenesis of primary S. aureus bacteremias in surgical patients who had undergone central venous catheterization, and we examined their respective risk factors.

Material and Methods

Study design. An observational prospective study was carried out through an active search system, based on spontaneous hospital demand, at Clinical Surgical Ward II of the Uberlândia Federal University Hospital (HC-UFU). Demographics, and intrinsic and extrinsic risk factors were recorded for each of the patients.

Microbiological techniques

CVC insertion site. The skin at the insert site of CVC was swabbed. Two samples were taken: the first, when the catheter was inserted and the second 5-7 days after insertion. Approximately 20 cm² of skin at the catheter insertion site was cleaned using sterile pre-moistened swabs. The swab was placed into an 1 mL tube with PBS + 0.1% of sodium thiosulphate, which agitated with a vortex, and about 0.1 mL of the fluid was inoculated on blood agar and mannitol salt plates. Skin cultures were considered positive whenever >200 UFC were isolated [9].

CVC tip. Catheters were removed under sterile conditions. The tips of the catheters were cut with sterile scissors and transported to the laboratory in tubes containing 10 mL of phosphate-buffered saline (PBS) + 0.1% Tween 80. The cultures of the catheter tips were examined quantitatively, using a modified Brun-Buisson [10] technique; a segment of approximately 5 cm of the catheter tip was placed in a tube containing 10 mL of PBS + 0.1% Tween 80 and agitated in a vortex for 1 minute; 0.1 mL of the liquid was inoculated in agar blood, McConkey agar and mannitol salt agar plates and incubated at 37ºC for 24 hours to determine the number of colony forming units (CFUs). Cultures were considered positive when > 10² CFU/mL were detected.

Hemocultures. Blood specimens were obtained through peripheral venous puncture. Hemocultures were performed by inoculating 5-10 mL of blood into a flask of the commercial automated system Bactec/Alert^® (Vitek System, Organon Teknika Corp. ). Positive culture flasks were sub-cultured in MacConkey agar and blood Agar, and plates were incubated at 37ºC for 24-48 hours.

Bacterial identification. Clinical specimens obtained from skin at the insertion site of the central vascular catheter tip were identified by classical techniques, being initially separated into Gram-negative and Gram-positive bacilli, Gram-positive cocci and yeast-form fungi and afterwards by their morphological/staining characteristics. Gram-positive cocci were subjected to complementary tests: oxidase, catalase, growth in NaCl, coagulase, mannitol fermentation and DNAse for the identification of S. aureus, coagulase-negative Staphylococcus (CoNS) and other Gram-positive cocci. Blood cultures were obtained from the microbiology lab of HC-UFU.

Antimicrobial susceptibility tests

Disk diffusion agar technique. Samples were cultured in TSB medium at 37ºC for 24 hours and then diluted in saline solution till the suspension opacity corresponded to the 0.5 tube of the MacFarland scale (1-2.10⁸ CFU/mL); they were then seeded with a swab over the medium surface [11]. The following antimicrobial discs were used: amoxacillin-clavulanate, rifampin, clindamycin, cephalothin, tetracycline, sulfametoxazole-trimethoprim, ampicillin, ciprofloxacin, gentamicin, vancomycin, chloramphenicol, erythromycin, quinupristin-dalfopristin, linezolide, and oxacillin. A standard sample of S. aureus ATCC 25923 was used as a control for the susceptibility test.

CR-BSI definition. Catheter-related bloodstream infection (CR-BSI) were defined as isolation of the same microorganism (i.e. identical species and resistance) from a semiquantitative or quantitative culture of a catheter segment and from the blood (preferably drawn from a peripheral vein) of a patient with accompanying clinical symptoms and no other source of infection.

Statistical analysis

The statistical analysis of risk factors for infection and microbiological results were performed by applying the ÷² test for comparing percentage values (qualitative variables) and the Fisher's exact test, when n was equal to or less than five. Risk factors and microbiological results were individually compared against a variable response (univariate analysis) with two by two contingency tables. Multivariate analysis through a logistic regression model were used for variables with high odds ratios. The Student's t-test was used for comparing means (quantitative variables). Statistical significance was defined as a p value less than 0.05. The analysis of variables was performed with statistical software SPSS PC version 11.0 (SPSS, Chicago) and Epi Info Software version 2000 (CDC Atlanta).

Results

Among 198 patients with a central vascular catheter inserted in the jugular vein (n=84) or a subclavia vein (n=114), 19 were withdrawn from the epidemiological analysis due non-recovery of catheter tips, removal to another unit, or hospital discharge, reducing the study to 179 patients. Four CR-BSIs caused by S. aureus were detected, another two were caused by MRSA. The CR-BSI rate caused by S. aureus was 4.9 episodes per 1,000 days/catheter and the CVCs colonization was 21.2%.

Risk factors analysis for catheter tip colonization are given Table 1. Evaluation by multivariate logistic regression analysis of risk factors associated with this contamination indicated the following: colonization at the CVC insertion site with > 200 CFU/20 cm² skin, internment >14 days, catheterization >7days and presence of erythema (Table 2).

Risk factors significantly associated with a CR-BSI: insertion site included: > 200 CFU/20 cm², > 10² CFU in the CVC tip, and presence of a multilumen catheter (Table 3). Based on the multivariate analysis, only bacteria at the insertion site (p = 0.03; OR = 6.89; confidence interval (CI) = 2.42-21.90) and in the tip (p = 0.01; OR = 7.95; CI = 1.95-19.60) were independent factors for CR-BSI (Table 4).

Microorganisms most frequently seen within SI, PC and blood are listed in Figure 1. The most frequent ones in SI were coagulase-negative Staphylococcus (49.7%) and S. aureus (31.2%), followed by Enterococcus (6.4%). In the microbiological analysis of the catheter tip, there was predominance of coagulase-negative Staphylococcus (60.5%) and S. aureus (28.9%), followed by Gram-negative bacilli (BGN) (7.9%). The frequency of isolates of S. aureus in the blood was greater than that of coagulase-negative Staphylococcus (41.4% versus 37.9%, respectively), followed by BGN (17.2%) and Enterococcus (3.5%). One hundred thirty-nine samples of S. aureus were isolated in these patients, 57 of which (41.0%) were MRSA and 82 (59.0%) MSSA. The phenotype MRSA was responsible for 37.1% and 36.4% of colonies at the insertion site and in the catheter tip, respectively, and they accounted for 50% of the BSIs caused by S. aureus.

Among MRSA isolates, multiresistance was the most commonly observed pattern, with simultaneous resistance to clindamycin, chloramphenicol, erythromycin, gentamycin, rifampicin, sulfametoxazol-trimetoprim, and tetracycline. Among MSSA samples, resistance to ampicillin, erythromycin and ciprofloxacin were more frequent. All the samples of S. aureus (MRSA/MSSA) were susceptible to dalfopristin/quinupristin and linezolide, as well as to vancomycin (Table 5).

Discussion

The incidence of CR-BSI varies considerably with the type of catheter, but most (90.0%) are associated with the use of short-term, non-tunnel CVCs, inserted into the internal jugular vein and the subclavia vein [12], which are the veins that we analyzed. The proportion of CB-BSIs varies from 2.5% to 6.4% [13-16], with rates corresponding to 2.4-12.0 episodes per 1,000 days/CVC [17-22]. We found a rate of 2.2%, or 4.9 episodes per 1,000 days/catheter, among patients that were not in the intensive-care unit (ICU).

A series of studies published in the 90's investigating CVCs that were not soaked with antimicrobial antiseptic gave a variation of the colonization rate for these catheters of from 23.6% to 52.2% in patients in ICUs [14-16,23-25]. In our study the colonization rate of CVCs was lower (21.2%).

Risk Factors associated with CR-BSI are numerous; they can be divided into intrinsic and extrinsic factors, with the following highlights: surgical services, prolonged hospital internment, ICU care, active infection at another site, underweight premature born infant, difficulty in inserting the CVC, high APACHE score, site of CVC insertion (internal jugular/femoral veins), type of bandage, skin colonization at the pericatheter site, duration of catheterization (>7/10 days), colonization of the catheter cannon, parenteral feeding, among others [22,26]. We found the following factors of risk to be significantly associated with CR-BSI: SI colonization > 200 CFU/20 cm² and > 10³ CFU on the catheter tip.

Studies have shown that an important factor of risk associated with PC and cannon colonization, is colonization of the pericatheter cutaneous site [27,28]. This colonization proved to be an independent risk for factor PC colonization in our study, as were internment time greater than or equal to 14 days and catheterization over seven days.

In CVCs lasting for less than eight days, catheter colonization is more commonly (75% to 90%) a result of extralumen migration of skin microorganisms to the catheter tip inside the blood vessel [22]. Colonization at the insertion site of 6.5-56.5 results in a relative risk (RR) for CR-BSI [26]. This observation suggests that bandages applied at this site can have considerable influence on the incidence of these infections [29-31]. In most infirmaries and units of the HC-UFU non-use of frequent occlusive bandaging prevails in this invasive procedure. Only 16 patients (8.9%) had occlusive bandages and 87.5% of them had <200 CFU/20 cm² on the pericatheter skin.

Most of the microorganisms implied in CR-BSI are part of the normal skin microbiota. Gram-positive cocci are responsible for, at least two-thirds of these infections [32]. Coagulase-negative Staphylococcus (Staphylococcus epidermidis) is the most common agent, followed by S. aureus, Enterococcus spp., Gram-negative bacilli and yeast-form fungi [33]. However, in our study S. aureus was the most frequent pathogen (38%), surpassing CoNS (34.0% and BGN (24.0%).

In an overview published in 2002 [34] about a series of prospective studies performed in the 90s, CoNS were the most frequently isolated microorganisms on the catheter tip, different from the blood, where the S. aureus was the most frequent. More recent studies confirm these findings [28,35]. In our investigation, CoNs frequently colonized the tip was (60%), while S. aureus was found in 30%; in the blood we saw a higher percentage of S. aureus (38%). The prevalence of S. aureus over CoNS in the blood was also reported by other investigators [36-38].

The microbiological diagnosis of a CR-BSI is very important, because its therapy will vary according to the isolated agent and according to its resistance spectrum. CoNS result in lower mortality rates than S. aureus, BGN, and Candida spp.[39,40].

Another important aspect about these infections is resistance to antimicrobial drugs, since many CR-BSI agents are resistant to routinely-used antimicrobials. Oxacillin-resistant CoNS and S. aureus infections are growing in frequency, especially within tertiary and/or school hospitals; they account for over 30% of isolates in some Brazilian hospitals, 34% in North-American hospitals and about 1.8-54.0% in European countries [41,42]. Among CoNS samples, isolates resistant to penicillin reach rates up to 85.5%[43]. In a previous study carried out at the HC-UFU, we found a frequency of 44% samples resistant to oxacillin amongst S. aureus isolates [44], similar to the 41.0% that we now have found.

MSRA isolates are usually resistant to several antibiotics, including betalactamics, aminoglucosides, macrolides, fluoroquinolones, chloramphenicol, mupirocin, and others; vancomycin is the drug of choice for treating severe infections by these microorganisms [45]. Recently, two new drugs, dalfopristine/quinopristine and linezolide, appeared as options for treating infections caused by MRSA [46]. In our investigation, we found an association of resistance to oxacillin in MRSA isolates showing susceptibility to vancomycin, dalfopristine/quinopristine and linezolide.

The routes of contamination by staphylococci of the CVC tip, with subsequent CR-BSI, are extraluminal in those of short lasting (<8 days) and intraluminal in those of long lasting (>8 days) infections; the blood stream is the most probable route in critically ill patients, as previously described [47]. In our study, the presence of microorganisms at the CVC insertion site was an independent risk factor associated with CVC colonization, showing the importance of the skin as a reservoir of this microorganism for CVC-tip colonization. In CR-BSI pathogenesis, while S. epidermidis and other CoNS usually adhere to the surface of the CVC polymer to form slime/glycocalyx after catheter insertion into the vascular system, in S. aureus the main mechanism of invasion is mediated by protein adhesins on the bacterial cell wall, involving fibrinogenic receptors and fibronectine in the biofilm of the CVC tip [48].

In the pathogenesis of CR-BSIs caused by S. aureus, the importance of nasal contamination by this microorganism is well established [49,50]. Sesso et al. [51] showed that nasal decolonization reduces the risk of pericatheter colonization eight-fold and CR-BSI four-fold. Nasal colonization by S. aureus in patients enrolled in our study was not assessed as a predisposing factor for this infection, but the presence of >200 CFU/20 cm² at the CVC insertion site was an independent risk factor for CR-BSI (OR=6.89). The bacterial load on the CVC tip is related to CVC culture positivity, and to finding of bacteria in blood culture and therefore to CR-BSI [52]. In our study, considering only cases of sepsis by S. aureus, > 10² CFU catheter tip colonization was a significant factor (OR=7.85), based on multiple logistic regression analysis.

The potential risk of not using occlusive bandages in the routine care of CVCs, which we found frequently in our investigation, also influences colonization levels at the CVC insertion site; it is associated with colonization on the catheter tip by S. aureus, an important factor in the pathogenesis of primary bacteremias.

Received on 06 December 2005; revised 22 March 2006.

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Publication Dates

• Publication in this collection
  21 July 2006
• Date of issue
  Apr 2006

History

• Accepted
  22 Mar 2003
• Received
  06 Dec 2005