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W4242702372 abstract "Introduction Despite improvements in measures for infection control, catheter-related infections remain relatively common in patients receiving intensive therapy. They are an important cause of bacteraemias and sepsis in the Intensive Therapy Unit (ITU), accounting for appreciable morbidity, prolonged ITU stay and higher costs of hospitalization. This article reviews the pathogenesis, microbial profile, diagnosis, management and prevention of this challenging ITU problem. Infections associated with central vein and pulmonary artery catheters now account for most episodes of bacteraemia in critically ill patients in ITUs [1]. This has resulted from the progressively increasing use of central lines for such purposes as haemodynamic monitoring, infusion of inotropes, fluids, electrolytes, antibiotics, and the provision of parenteral nutrition. Catheter-related infection remains a serious and potentially lethal complication in critically ill patients. Definitions and epidemiology No worthwhile statements can be made about incidences of catheter-related infection, its predisposing factors and the effects of preventative measures unless there are first some workable definitions of terms. The term 'sepsis' has generated much controversy but is now recognized as referring to the systemic inflammatory response to severe infection [2,3] whether or not an infecting organism can be identified. The definition of 'catheter-related infection' is also controversial [4]. According to the most widely accepted definition, it is bacteremia (with or without the signs of sepsis) that is attributable exclusively to a central catheter [5]. The diagnosis requires the isolation of the same pathogen in cultures taken from peripheral blood and from specimens more specifically related to the central catheter (catheter tip, swab from insertion site, or blood taken through the catheter) in the absence of any other identifiable infective source [4]. Maki et al.[6] defined 'local catheter-related infection' as a colonization of the intravascular portion of the device from which positive semi-quantitative cultures with more than 15-colony-forming units (cfu) can be obtained. Reed et al.[7] used the term 'site infection' which refers to the presence of pus at the insertion site and/or of ≥ 15 colonies on semi-quantitative culture or ≥ 103 on quantitative culture of the intracutaneous (proximal) catheter segment; site colonization denotes <15 or <103 colonies. 'Catheter-related bloodstream infection' is defined by the combination of: (a) clinical signs of sepsis; (b) a positive semi-quantitative culture of the catheter tip or of the introducer sheath; (c) at least one percutaneously drawn blood culture positive for the same strain; and (d) negative cultures of the infusate [6]. 'Catheter-related sepsis' can be defined by the coexistence of signs of systemic inflammatory response and the presence of a demonstrably colonized catheter, but in which there is no positive blood culture, as might happen in a patient who is already on antibiotics. We might also use the term 'catheter-associated', instead of 'catheter-related' infection or sepsis to denote the absence of clear evidence that the catheter is solely responsible for a bacteraemia or the signs of sepsis. An estimated 12% of all nosocomial infections in ITUs are bacteraemias or fungaemias [8] of which about 16% are reportedly associated with intravascular catheters [9]. Estimates of the absolute incidence of catheter-related bacteraemia vary widely, partly no doubt from laxity of definition, partly from variation in case load, and partly from variations in practice. For instance, 2.1 per 1000 central-catheter days have been reported for ITUs limited to respiratory support, whereas 30.2 per 1000 central-catheter days have been reported for ITUs that deal with burns [10,11]. Patient-related predisposing factors that can underlie variation in incidence are listed in the section headed 'risk factors'. Microbial profile and pathogenesis The most commonly isolated pathogens in infections related to central venous or pulmonary arterial catheters have been coagulase-negative Staphylococcus (mainly Staphylococcus epidermidis) (20% to 96%) or Staphylococcus aureus (5% to 40%), while Gram negative bacteria (20% to 33%) and Fungi (8% to 22%) have been reported more often in recent years [11-14](Table 1). Coagulase negative Staphylococcus epidermidis is a common pathogen which usually produces a slime that provides strong protection against phagocytes and antibiotics, and thus facilitates the development of infection or sepsis [15]. The production of slime has been suggested to be a marker of pathogenicity of Staphylococcus epidermidis in catheter-related infections [8].Table 1: Microbial profile of catheter-related infections Central catheter-related infection is usually because of contamination of some portion of the catheter (external, subcutaneous or intravenous (i.v.)). Organisms colonizing the patient's skin at the insertion site are the most frequent contaminants of the catheter [16], by migration along the catheter track to the catheter tip [17](Table 2). Skin contamination at the insertion site is therefore a fundamental risk factor for catheter-related infection and sepsis [18]. It is notable that, in 80% of cases, the same pathogen is isolated from cultures of peripheral blood, catheter tip and the skin at the insertion site [19].Table 2: Pathogenesis of catheter-related infections Contamination of the catheter hub is another common source of catheter-related infection, and seems to be strongly associated with frequent manipulations by medical and nursing staff [20]. A strong association has also been found between pathogens isolated from cultures of the catheter hub, catheter tip, and peripheral blood [21]. Another cause of catheter-related infection is microbial contamination of the entire system (transducers, connectors etc.) connected to the central line [22]. Haematogenous contamination [23] may also occur with enterobacteriaceae and fungi as the predominant pathogens [24], but this condition does not constitute central venous catheter-related infection because its definition excludes the possibility of any other identifiable infective source. Presumably, it represents a secondary central-catheter infection. Contamination from the infusate is rare [19,25](Table 2), but when it does occur, it is liable to do so as an epidemic, the most common pathogens being Gramnegative bacteria (Pseudomonas species, or enterobacteriaceae, or Serratia etc.). The most severe infections occur when thrombi surrounding the catheter become infected, thus causing septic thrombosis of the central vein or the pulmonary artery [26,27]. With septic thrombosis, the central vein or the pulmonary artery becomes an 'abscess', discharging pathogens into the bloodstream. The resulting bacteraemia or fungaemia is persistent and usually produces the signs of sepsis. Signs of major central vein occlusion may become apparent (e.g. swelling of the corresponding side of the face, neck and upper limb). Risk factors The risk factors (Table 3) include the type and material of the catheter [28-30], the duration of catheterization [31], the site and mode of insertion [32], the subsequent management, concurrent presence of infection [33,34] and the patient-related factors. (Table 4)Table 3: Risk factors of catheter-related infections Table 4: Diagnosis of central catheter-related infection Types of catheter Commercially available central catheters vary in their component materials, their design and their intended mode of use. Several plastic materials are in use, including polyethylene, polyvinyl chloride, silicone and polyurethane [35]. Some are coated with antiseptic or antibiotic, some are heparin-coated or bonded and some may have a collagen cuff intended to obstruct the migration of skin organisms. Catheters may have single or multiple lumens and may be inserted from central or peripheral access sites. They may be inserted after surgical exposure of the central vein (particularly in paediatrics) though percutaneous insertion is usually the first choice, with or without subcutaneous tunnelling to extend the length of subcutaneous track between insertion site and the tip. The purpose of central catheters may be simply for haemodynamic monitoring, or to infuse non-nutrient solutions (crystalloid or colloid) for volume replacement or as vehicles for drugs, or to give blood or nutrient solutions for total parenteral nutrition. Though they are not primarily the subject of this review, large centrally placed catheters are increasingly being used as the input and output ports for the partial excracorporeal circulation that is required for haemo(dia)filtration to support defective renal function, and more rarely for modalities of extracorporeal exchange of respiratory gases to support catastrophic pulmonary failure. Polyethylene catheters are particularly prone to bacterial adherence, while siliconized stainless steel needles have the lowest incidence of catheter-related infections [36]. A significant decrease in infections has been reported with antiseptic- or antibiotic-coated central catheters [37,38]. The presence of an antibiotic or antiseptic agent in the lumen and on the external surface of the catheter, has been found to prevent adherence of the pathogens and significantly decrease the risk of catheter-related sepsis. Thrombosis and contamination of the catheter is also reduced when the external surface of a central catheter is heparinbonded [39]. Good results have also been reported by some with catheters carrying a collagen cuff [40,41], but this has been contested [42]. A significantly higher infection rate has been found with triple-lumen as opposed to single-lumen catheters [43,44], though this may well be related as much to the different uses to which they are put as to the catheters themselves. Site and mode of catheterization There is no difference in overall infection rates between peripheral and central routes of catheter insertion [45,46], but the incidence of central venous catheter-related infection has been shown to depend on the vein that is catheterized, with higher incidence for the internal jugular than the subclavian vein [47,48]. Significant operational risk factors for central catheter-related infections are the difficulty and the number of attempts at catheter insertion, and a requirement for surgical cut down instead of percutaneous insertion. There have been conflicting results from comparisons of the infection risk when using a Seldinger technique for catheter insertion [49,50]. Conflicting results have also been reported from comparisons using transparent semi-permeable or sterile dry gauze dressings at the insertion site [51,52]. The transparent dressing allows continuous inspection of the insertion site for evidence of inflammation, and an early report of an associated increased frequency of infections [53] has recently been refuted [6]. The risk of central catheter-related infection and sepsis is also associated with the duration of catheterization [31]. Several studies have shown a significant increase in catheter-related infections after the 4th day. The risk with time must be accentuated by frequent manipulations of the hub and connections to the catheter that are an inevitable part of the mode of use of many catheters [20]. A particular manipulation of the catheter itself deserves consideration. It is the practice in many ITUs of guiding a new replacement catheter through the track of an old catheter that has just been removed over a Seldinger wire ('rewiring a catheter'). Logically there should be concerns over potential displacement by the wire of any intraluminal colonization from the first catheter, or of displacement pathogens from the catheter track by the new catheter, or of early colonization of the new catheter by the organisms that had occupied the track of the old. This theory has been supported by several studies [54,55]. Patient-related factors Predispostion to catheter-related bacteraemia is recognized in the elderly [13] as well as in neonates and in infants of low birthweight [56-58]. The likelihood is greater in the presence of concurrent diseases such as infection [59], malignancy [60-62], chronic renal failure [63,64], acquired immunodeficiency syndromes [65,66] and haematological disorders [67]. Catheter-related infection is also more likely with certain types of treatment - in patients requiring tracheostomy [68], or receiving immunosuppressive treatment [69], chronic haemodialysis [64] or parenteral nutrition [70-74]. In most cases, several factors will be acting in concert. For instance, patients receiving total parenteral nutrition are often severely ill and immuno-compromised: they consequently have at least one catheter in place for a prolonged period, and receive through it a hypertonic infusate that tends to cause catheter-thrombosis which supports the growth of pathogens. The increased infection rate in patients who are submitted to chronic haemodialysis is because of, not only the patient's immunosuppression, but also the use of large, rigid catheters that are subjected to frequent manipulations by medical and nursing personnel. Operator-related factors There is a well-documented inverse relation between experience of the operator and catheter-related infection [54,75]. The use of strict barrier precautions (sterile dressings, surgical masks and gloves, disinfection of skin at the insertion site) carries a significantly lower risk [76]. Some hospitals employ special teams for management of central catheters but it remains to be determined whether this has any preventative impact. Diagnosis There are no very specific clinical symptoms or signs of catheter-related sepsis, so that clinical detection and diagnosis is often very difficult. The clinical diagnosis is based on the presence of fever, chills, leukocytosis, exit-site inflammation (especially if it is purulent) in a patient with at least one central catheter and with no other apparent source of infection. The primary symptom, fever, is present non-specifically in patients, whereas the more specific signs of local inflammation are evident in only 35 to 50% of the cases. Microbiological confirmation is therefore highly desirable. It increases the specificity, but the sensitivity of bacteriological diagnostic criteria is usually affected by antibiotic treatment that may already have been instigated for infections from other identified sources. Thus, it is sometimes necessary to stop previous antibiotics before carrying out culture to avoid reducing in vitro sensitivity. Simple Gram-stain of the catheter tip is a rapid, sensitive method for diagnosis of an infected catheter [77]. Culturing the subcutaneous part of the catheter is better correlated with bacteraemia than cultures of the i.v. segment [40]. Semi-quantitative culture of the catheter tip is the most specific and reliable aid to diagnosis. Maki's technique is the most commonly used because it is rapid, simple and economical [78,79]. It involves rolling the catheter tip over a blood agar place, incubating the plate and counting the colonies of pathogens [80]. The diagnostic criterion propounded by the Center for Disease Control and Prevention (CDC) in the United States is a count of more than 15 colonies [81,82] though some authors use five colonies as the cut-off [83,84]. If there are fewer than 15 colonies the diagnosis (according to the CDC) is a simple contamination. The acridine orange leucocyte cytospin (AOLC) test or acridine orange stain of the intravascular segment of the catheter is a rapid and an adequately sensitive and specific method in the diagnosis of catheter-related infection, showing excellent correlation with quantitative culture techniques. Red cells are lysed with hypotonic normal saline. The leucocytes are pelleted by centrifugation, a cellular monolayer is prepared from the pellet in cytospin and slides are stained with acridine orange and examined by an ultraviolet microscopy. A positive result is the detection of bacteria [85]. Another diagnostic method, helpful in distinguishing contamination from infection of intravascular inserts, is Cleri's technique for the quantitative culture of the intravascular insert [86]. This simple technique is carried out by flushing the catheter with broth. The criterion for diagnosing infection is that there should be more than 103 colony-forming units. Isolation of the same pathogen in the catheter tip and blood cultures is highly suggestive of central venous catheter-related infection or catheter-related bloodstream infection. Positive peripheral blood cultures from at least two different sites (in addition to catheter-related cultures) should be a condition for starting antibiotic treatment. Catheter-related infection is more probable when the organisms in the blood are Staphylococci (especially coagulase negative) or Gram-negative bacilli, but less probable when E. Coli or anaerobes are isolated. Negative blood cultures are of limited value because the bacteraemia may be transient, and may be masked by current antibiotic therapy. Blood cultures taken through the central catheter are frequently contaminated [87], but a catheter-related infection can be confidently diagnosed if blood cultures withdrawn through the catheter are positive for the same organisms as, but with five times more colonies than, cultures of peripheral blood [88]. Positive quantitative culture of the skin at the insertion site usually confirms the diagnosis of catheter-associated infection, especially in the presence of local purulent discharge [89]. The diagnosis is more likely when greater than 50 cfu of coagulase-negative Staphylococci are isolated in skin cultures [13]. Despite all the clinical and microbiological care that may be put into diagnosis, an appreciable proportion of suspected catheter-related infections will not be definitively diagnosed until after the catheter has been removed and the septic condition has resolved. Management Any diagnostic difficulty contributes to the dilemma of managing actual or suspected catheter-related infections. Central catheters are no luxury in the sorts of patients who are more likely to acquire catheter-related infections. Though removal may be the only way to solve the catheter-related problem, it may also temporarily deprive a patient of therapy that is indispensable. In patients whose ITU stay has been long and problematical, it may be no easy task to find an alternative central venous access and, if another catheter is successfully inserted before any bacteraemia has been cleared, it too may become infected. This is especially so if a new catheter is 'rewired' into the place of the previous one, in which case there is no time for clearance of the bacterial contamination of either bloodstream or catheter track. There are no data on how long ought to be allowed for clearance. However, this approach of guidewire exchange of the catheter should be avoided if signs of infection such as pus, heat, erythema exist at the insertion site. When local signs of infection are absent, but the patient is febrile or there is clinical evidence of sepsis (without any other identifiable source of infection) a guidewire exchange of the central catheters can be carried out. In this case, the culture of old catheters is strongly recommended, and if positive, the new catheters should be removed. When there is strong suspicion that fever and signs of sepsis are because of a central venous catheter infection, and when no other source is identifiable, the first step before starting antibiotic therapy should undoubtedly be to remove all catheters and carry out Gram stain and cultures of the peripheral blood and catheter tip. In many cases, simple removal of catheters may result in resolution of infection. If fever and leukocytosis persist, antibiotics should be instituted or changed if the patient is already on antibiotic therapy. Appropriate empirical antibiotic therapy may be used until the results of blood or catheter tip cultures are obtained. The empirical antibiotic therapy should be directed against the most common pathogens (Staphylococcus aureus or epidermidis or Gram negative bacilli). For this reason, a combination of an anti-staphylococcal antibiotic and a second generation cephalosporin is the preferred choice. When a pathogen is isolated, antibiotics should be altered based on sensitivity testing [90]. The duration of antibiotic administration is usually 5 to 10 days (Table 5).Table 5: Management of catheter-related infection It should be emphasized that strains of the most frequent pathogens in catheter-related infections (Staphylococcus epidermidis) are usually resistant to semisynthetic penicillins or cephalosporins [23]. The drug of choice is teicoplanin (6 mg kg−1 day−1) which is as effective as vancomycin (2 g day−1), but is not commonly nephrotoxic and does not cause 'red man' syndrome [91,92]. Alternatives are rifampicin (600-900 mg day−1) or fucidic acid (1.5-3 g day−1) for cases in which vancomycin or teicoplanin cannot be given. Patients with catheter-related infections as a result of Staphylococcus epidermidis, should receive a short course (3 to 5 days) of antistaphylococcal therapy or until they are afebrile for 48 h (although simply removing the catheters may be adequate especially in patients with competent immune systems). For methicillin-sensitive Staphylococcus aureus, a synthetic antistaphylococcal penicillinase-resistant penicillin is recommended. Alternatives are a first generation cephalosporin, clindamycin, erythromycin, ticarcillin clavulanate or a quinolone. For methicillin-resistant Staphylococcus, the first choices are teicoplanin (6 mg kg−1 day−1) or vancomycin (2 g day−1). Alternatives are rifampin (600-900 mg day−1) or fucidic acid (1.5-3 g day−1). For Stapylococcus aureus, the duration of the i.v. therapy should be at least 2 weeks, because of the high frequency of metastatic infectious complications, especially when foreign bodies have been inserted [93]. Garrison and Wilson advocated that the duration of antistaphylococcal therapy must be at least 4 to 6 weeks because of the persistent nature of these pathogens and the increased risk of subsequent endocarditis [13]. The duration of antibiotic therapy is prolonged in the presence of endocarditis or septic thrombosis. For Gram-negative bacteria, imipenem (2-4 g day−1), a third generation cephalosporin, a quinolone (800 mg day−1) and an aminoglycoside are used either individually or in combination [94]. Ticarcillin clavulanate (12.8-9.2 g day−1), aztreonam (3-8 g day−1), piperacillin (9-16 g day−1) or piperacillin tazobactam (18 g day−1) are good alternatives. When a fungus is isolated at the catheter tip, removing the central catheters may be adequate. However, there is considerable evidence that all ICU patients with candidaemia should be treated, even if their fever resolves after the removal of the catheter, because catheter-related candidaemia often leads to disseminated infection [95]. These patients should receive systemic antifungal therapy for 3 to 6 weeks [96]. Rarely should therapy be for less than 4 weeks and, in very ill patients, should be considerably longer (8 to 10 weeks) [97]. Although amphotericin B (0.3-0.8 mg kg−1 day−1) has long been the standard treatment of candidaemia in patients without neutropenia or severe immunodeficiency, fluconazole (200-400 mg day−1) is a good alternative [98,99]. Available clinical data suggest that fluconazole is as effective as, and better tolerated than, amphotericin B, in the management of systemic fungal infections [100]. Catheter-related septic central vein thrombosis should be treated with a combination of parenteral antimicrobial (for 4 to 6 weeks) and anticoagulation with heparin [11]. Prevention Preventative measures require meticulous care with all aspects of catheter management, beginning crucially with reducing skin colonization at the insertion site, careful choice and placement of catheter, optimal subsequent management of the insertion site, avoidance of manipulations of catheters delivering high-risk infusions such as parenteral nutrition, and extreme care with unavoidable manipulations of catheters, infusion systems and the infusates that are connected to them [11]. Disinfection of the skin at the insertion site before catheter placement is probably the single most important issue in prevention. Several chemical antiseptics are widely used, and due attention must be given to the time that must be allowed to enable them to be effective (e.g. 30 s for 70% alcohol or 4 min for 10% povidone-iodine). Antimicrobial or antiseptic ointments are also used to cover the catheter insertion site in an attempt to prevent colonization on the skin, but their effectiveness remains to be established [12,101,102]. Promising results from clinical trials showing benefit from coating catheters with antibiotic or antiseptic agent [38,103,104] have yet to make a convincing impact on clinical practice. Early studies [51,52,53] generated doubt about whether transparent polyurethane film prevented or promoted infection, compared with dry gauze dressings, but a recent study by Maki et al. found no significant differences in rates of catheter colonization or catheter-related bloodstream infection between groups having catheters dressed with sterile gauze, conventional polyurethane dressing, or with a highly permeable polyurethane dressing [6]. Another critical issue is the duration for which the catheter remains in place. It is generally desirable for central venous catheters to remain in place until their function is no longer deemed necessary or until there is good evidence, or at least strong suspicion, that they have become infected. No benefit has been demonstrated in routinely changing the central catheter [105]. However for pulmonary artery catheters, there are good reasons to limit the duration of placement strictly to no more than 4 days [6,11]. The use of strict protocols for the insertion and care of catheters, and, for the care of the insertion site, and the routine replacement of i.v. giving sets every 24-48 h, have been reported to significantly decrease the rate of central vein catheter-related infections. Good results have also been reported when dressings are changed routinely (three times per week). On the contrary, the use of microfilters positioned between venous catheter and infusion line has not been shown to reduce the rate of catheter-related infection [106]. The use of central catheters for drawing blood samples and the manipulation of giving sets, transducers and stopcocks should be minimized. Infection rates are significantly lower if central venous catheters that are used for parenteral nutrition are used exclusively for that purpose. Nutritional support teams have been developed in several institutions to undertake professional responsibility for nutritional support of the patient, including ensuring the sterility as well as the nutritional appropriateness of the solutions and the safe maintenance of the feeding catheters. Several investigations have shown the effectiveness of nutritional teams in preventing infections in ITU [107]. Time and trouble spent in preventing catheter-related infections will be amply repaid by savings of effort and resources in diagnosing and managing avoidable infections, and by reductions in mobidity and mortality in ITU patients." @default.
W4242702372 created "2022-05-12" @default.
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W4242702372 date "1996-09-01" @default.
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W4242702372 title "Central venous catheter-related infections" @default.
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