How to Prevent Infections in Intensive Care ?
Intravascular catheters are widely used especially in intensive care units for fluid replacement, parenteral nutrition, blood and blood product transfusion, drug applications and hemodynamic monitoring. However, catheter use causes infectious and noninfectious complications. The risk of catheter infection is 1-2 / 1,000 catheter days. Intravascular catheter infections are important causes of morbidity and mortality. Coagulase-negative staphylococci, Staphylococcus aureus, enterococci, aerobic gram-negative bacilli and Candida albicans are the most common microorganisms that cause catheter infection [1] . The treatment of catheter infection varies according to the catheter used, the type of infection developed and the causative microorganism [2] . Therefore, the definition should be made well ( Table 1 ) [1-4] .
DIAGNOSIS
Clinical Diagnosis
The sensitivity and specificity of the clinical findings are low in catheter infection. Catheter infections are clinically seen as skin infection, subcutaneous tunnel infection, thrombophlebitis, bacteremia, sepsis, infective endocarditis, metastatic infections (diffuse abscesses, osteomyelitis, septic arthritis) [3,5,6] . Catheter infection may present with local and / or systemic symptoms.
Local infection findings: Inflammation at the site of catheter entry is one of the most common signs of infection. Redness, heat increase, pain, and exudate are encountered around the catheter exit site. Phlebitis develops in up to 30% of patients with a peripheral venous catheter, but catheter-related infection occurs in up to 10% of cases [3,6] . In tunneled, long-term catheters, such as Hickman-Broviac catheters, exit site infection can spread through the catheter (over an area greater than 2 cm), causing cellulite [3,4] . Inflammation, fluctuation and cellulitis around the implanted port, and sometimes necrosis in the skin covering the port [1,3-5] .
Systemic findings: Fever, chills, tremor and bacteremia may lead to septic shock. Hypotension, hyperventilation, respiratory failure, abdominal pain, vomiting, diarrhea, confusion, convulsions may occur in patients going into shock [3,5-7] .
Peripheral or central septic thrombophlebitis may be accompanied by chills, chills, fever and shock; this is especially the case in gram-negative bacilli infections [3,5,6] . Conditions suggesting catheter-related sepsis are summarized in Table 2 [1-6,8] .
Shock occurs more frequently when the infusate is contaminated and has a fulminant course; however, these findings are not common in catheter-related infections [3,5,6] .
Embolic events or other signs of metastatic infection may occur (such as Candida endophthalmitis) [5,6,9] .
Laboratory Diagnosis
Clinical findings (evaluation of local and systemic findings in patients with catheters) and microbiological studies are two important aspects of the definition.
In some cases, radiological investigations are also applied (investigating thrombotic / embolic events: radiographs, ultrasonography (USG), computed tomography (CT), radiological evaluation after venous catheter administration or venous Doppler USG study showing fibrin formation or intra-lumen narrowing. may contribute to the diagnosis of catheter infection [9-11] .
Gram Staining
Gram and acridine staining from catheter discharge is helpful in rapid diagnosis, but its sensitivity is low compared to quantitative methods [12,13] .
Catheter Outlet Culture
Swab culture from the catheter outlet site predicts catheter-related infection by 66%; the absence of reproduction in the culture indicates that the catheter culture would be 97% negative [6,11,14] .
Catheter Culture
The catheter can be semi-quantitative (Maki method) or quantitative (sonication method) culture; they are more specific than qualitative cultures. The predictive value of quantitative and semi-quantitative cultures varies according to the type, localization, type of culture and source of colonization. In the semi-quantitative culture, the tip of the catheter is rolled onto the media surface and ≥15 colony bacteria growth is significant in the culture after a 24-48 hour incubation period [1,4,6,11,15,16] . To assess the bacteria in the catheter lumen, 1 mL of tryptic line broth is sonicated in the catheter or sonicated in the broth, followed by seeding after 100 consecutive dilutions. At the end of 48-72 hours of incubation at 35 ° C, 10 2 or more colonies are indicative of catheter infection. With this method, it is possible to reach not only microorganisms that are on the outer surface of the catheter, but also lumens and biofilm adherent microorganisms, and sensitivity and specificity have been found to be generally 80-90% in the studies and it is a sensitive method especially for catheters that remain in place for more than 1 week. 20% more sensitive than the method [1,5,7,14,17] . Bacterial growth 18-24 hours after the catheter tip is simply thrown into a liquid medium does not give specific results due to the possibility of contamination during removal and this seeding method is not preferred [1,14,15] .
If the catheter is not removed, Gram staining or quantitative culture of the catheter outlet smear together with catheter hub cultures may help to diagnose.
Another method that does not require catheter removal is to take the sample through the kat brushing içinden technique, allowing the biofilm in the catheter lumen and the microorganisms attached to the thrombus to the end to be grown and cultured in culture; however, this method has a 6% risk of transient bacteremia [5,18] .
Blood Cultures
At least two sets of blood cultures should be taken from patients with suspected catheter-related infections. In case of suspected catheter infection, quantitative culture is performed from the blood taken from a peripheral vein with the relevant catheter lumen or the reproduction time of blood cultures taken from automated systems is monitored. Skin antisepsis should be considered when taking blood culture, contamination can lead to misleading results. The positive predictive value of catheter and peripheral venous blood culture for catheter infection was 63% and 73%, respectively; negative predictive value is 99% and 98%, respectively [19] .
If the number of colonies detected in the culture of catheter blood is 5-10 times higher than the culture of peripheral venous blood, the diagnosis of catheter infection is made. In automated systems that detect reproduction by signal, catheter blood reproduction is 2 hours before the peripheral vein blood sample, indicating catheter infection; sensitivity and specificity of this method have been reported as 91% and 94%, [1,4,7,8,11,14,20] . Simultaneous blood culture from catheter and peripheral blood allows diagnosis and selection of appropriate treatment in Hickman Broviac or subcutaneous central venous catheters without catheter removal. A single positive blood culture is important for the diagnosis of candidemia [2] .
Bacteremia due to infusion fluid is rare. The growth of the same microorganism in infusion fluid and blood culture is diagnostic. Clinical manifestations immediately after infusion suggest bacteremia due to infusion fluid.
PROTECTION
Catheter-related precautions and catheter-related infections can significantly reduce catheter-related infections and bacteremia. Risk factors associated with catheter infections should be considered at the point of prevention ( Table 3 ) [4,6,21] .
Catheter Indication
For catheter insertion, it should be indicated first.
1. Inadequate venous access,
2. Requires long-term total parenteral nutrition (TPB) or chemotherapy,
3. Venous sclerosing agent application,
4. Indication of catheter insertion in emergency situations.
Unnecessary catheter application should be avoided and the catheter removed when the indication ends [4] .
Infusion Treatment Team
Written rules on infusion therapy and catheter use should be established and updated regularly. A team of pharmacologists, infectious diseases and clinical microbiologists, nurses and physicians performing intravenous (IV) interventions may be involved in the preparation of guidelines and guidelines. Special IV treatment teams can be established for IV interventions. The formation of experienced infusion treatment teams can reduce the catheter-related infection rate by 8-10 times. Especially in centers with a high incidence of catheter infections, it is more economical to appoint an infusion treatment team. In the absence of a team to monitor the event at all levels, relevant health personnel should be trained at regular intervals [4,22,23] .
Selection of Catheter Type and Place of Application
Catheter type and site are effective on the risk of infection development ( Table 3 ). For example, the rate of infection in central venous catheters is higher than in peripheral venous catheters; in adults, the venous catheter to the lower extremity (femoral) is more risky than the upper extremity (subclavian <jugular) [21] . In the upper extremity, the risk of infection in the upper hand veins is lower than in the upper arm and elbow. On children's hands and feet or scalp may be preferred. Infection in peripheral venous catheters is lower than central venous catheters. For central venous catheter insertion, the risk of infection in the subclavian vein is lower than in the jugular and femoral vein. If there is no contraindication, the subclavian vein should be used instead of the jugular and femoral vein [24] . It should be noted that down cut-down dı increases the risk of infection. Multi-lumen catheters should not be used unless specific indications, as they are more infected. Multi-lumen catheters are useful when different fluids such as long-term high-dose chemotherapy, blood products, total parenteral nutrition (TPB) are required. If a multi-lumen catheter is used, a lumen should be reserved for hyperalimentation [24] . Multi-lumen and multi-purpose catheters have a high risk of developing infections, so these types should be avoided as much as possible [4,22,23] .
The catheter should be chosen with the lowest and most economical risk of infection according to the treatment considered, and the catheter should be removed immediately after the indication is eliminated. The construction material is also important in the selection of the catheter. Polyvinyl chloride and polyethylene catheters have a higher risk of thrombosis and infection than teflon, silicone and steel titanium catheters [4,23] .
Many microorganisms (staphylococci, candida) show more adhesion than polyvinyl chloride catheters, polyurethane and teflon catheters. There is a greater risk of mechanical complications (obstruction, thrombosis, leakage, displacement) with polyvinyl chloride catheters. The risk of infection in steel needle use is similar to that of Teflon catheters. However, irritant IV fluids used from steel needles can escape into subcutaneous tissues and cause complications. Steel needles should not be used in cases where such fluids should be given [4] .
Dacron cuff in non-implanted catheters causes inflammatory reaction and fibrosis. Dacron cuff does not prevent the development of infection [22] .
Central venous catheter (SVC) or peripherally inserted SVC (PSVC) should be used if treatment longer than 30 days is required in patients older than 4 years. Tunneled or implanted catheters should be used when longer treatment is required [24] .
Catheter Installation
Maximum barrier and asepsis precautions should be taken during catheter insertion. Particular attention should be paid to the rules of asepsis (hand washing, long-sleeved sterile shirt, mask, cap, large sterile drape, sterile gloves ...), especially when inserting a central venous catheter [6,23,25,26] . Using local antimicrobials (mupirocin, chlorhexidine), washing the catheter lumen with antibiotics, using catheters with antiseptics or antibiotics, and tunneling are among these measures [2,4-6,22,23,27-29] .
In case of insertion or removal of catheter, daily examination of catheter insertion area, before and after dressing, hands should be washed. Water, soap, antiseptic soaps or alcohol-based gels can be used in hand washing [30,31] . Sterile gloves should be worn after handwashing during catheter insertion / removal [4,22] .
The most important point during catheter insertion is skin cleaning; 2% chlorhexidine, 10% povidone iodine and 70% alcohol are more effective for this purpose [25] . Povidone iodine may be used in patients with chlorhexidine allergy. If povidone iodine is used, it should be applied for 3 minutes and iodine should be allowed to dry. The use of post-iodine alcohol in povidone prevents irritation. Organic solvents such as acetone should not be applied to the skin before catheter insertion. In addition, routine administration of antibiotic pomades instead of catheter access is not recommended [24] .
The bristles at the catheter inlet can be cleaned, but should not be shaved. It is useful for patients to bathe with disinfectant before catheter insertion. After skin cleansing, the entry site should not be palpated (palpable if working in a sterile area).
Catheter Care
Catheter infection rates (infection per 1,000 catheter days) are monitored by regular surveillance. In this context, variables such as catheter wearer (s), catheter insertion time, catheter insertion site, catheter type, treatment administered, and catheter removal time should be processed and evaluated on surveillance forms. Complaints and symptoms related to catheter infections should be evaluated daily and necessary diagnosis and treatment procedures should be performed in case of suspected catheter infection [4,6,22,23,29] . An intravenous catheter should be applied and the patient should be examined daily. Wound dressing should be performed after catheter insertion. Porous adhesive dressings should be used instead of occlusive dressings. Good quality sterile gauze is used for dressing; In recent years, transparent, semi-permeable and polyurethane dressing has been increasing in practice [4,22] . The dressing of the peripheral catheters can be changed every 72 hours. It is reported that this period can be extended up to 7 days [31] . The dressing should be changed when the catheter is altered, removed, or when the dressing is contaminated, wetted, loses its sealing ability, and bleeding occurs [22,24,31] . Wash hands before and after dressing change. Sterile or clean gloves should be used when changing dressings [30].
Catheter Insertion Time and Replacement
Peripheral venous catheters should be replaced after 72-96 hours, and if the catheter is inserted in an emergency, it should be replaced within 48 hours [30] . The catheter can be left in place as long as there is no sign of inflammation in children and the catheter works. Artery catheters can be left in place for 6 days and pulmonary artery catheter for 5 days; suitable for longer periods in children. Leaving catheters in place longer than the specified periods increases the risk of infection. The total parenteral feeding catheter may remain in place for up to 30 days [4,22] . Routine replacement of central venous catheters has no role in preventing catheter infection.
The IV administration sets do not need to be replaced before 72 hours unless otherwise indicated. There was no difference in the risk of infection between the replacement of peripheral catheters at 72 hours and at 96 hours [30] . If blood, blood products, lipid solutions have been administered, IV administration sets should be changed at the end of the infusion or within 24 hours.
Catheter hubs and ports should be cleaned with alcohol, chlorhexidine or povidone iodine prior to drug administration [21] . Sterile syringes should be used in every attempt.
Washing Solutions and Anticoagulant Usage
In long-term catheters, there are various recommendations for washing the lumen with washing solutions and anticoagulants. The use of heparin for this purpose prevents the development of thrombophlebitis, but facilitates coagulase-negative staphylococcal growth in catheters. The use of EDTA reduces the risk of infection due to coagulase-negative staphylococci. In high-risk patients, washing with EDTA and minocycline may prevent recurrent catheter infection [4,22] . Low-dose warfarin prophylaxis is useful in preventing thrombosis in patients on long-term intravascular catheters [21] . Patients should be educated verbally and in writing about catheter care and hand washing.
Filters
Filters prevent the passage of contaminated liquids. It reduces the risk of phlebitis due to infusion. It prevents the passage of gram-negative microorganism endotoxins. However, fluids such as dextran, lipid, and mannitol can lead to clogging of the filters and reduce the efficacy of drugs, so the use of filters for infection control is not recommended routinely [30] .
Antibiotic Prophylaxis and Antibiotic Catheters
Although antibiotic pomades administered during and after catheter insertion may prevent the development of infection, they increase the risk of Candida colonization; mupirocin administration, for example, reduced internal jugular catheter colonization by 5-fold; but the same effect was not observed in peripheral vein and artery catheters; and the use of prophylactic mupirocin has led to selection of resistant strains. Antibiotic pomades are not recommended for catheter dressing applications at additional costs [6,22,23,27,29] . Systemic antibiotic prophylaxis is also not required. The use of prophylactic glycopeptides may cause selection of resistant microorganisms [21] .
Antibiotic (vancomycin / teicoplanin, minocycline + rifampin), antiseptic (chlorhexidine, chlorhexidine + silver sulfadiazine) coated catheters have been shown to reduce the risk of infection with antiseptic hub administration [23,28,29] .
The use of antimicrobial-containing catheters may lead to the development of resistance to the antibiotics used [32] . The duration of protection in antimicrobial catheters was reported to be 14 days. In this context, it is recommended to limit the use of such catheters in cases where infection rates and risk of sepsis are high. Antibiotic catheters should be used when short-term (<10 days) catheter insertion and at risk of catheter-associated bacteremia (total parenteral nutrition, immunodeficiency, intensive care stay) and if the catheter will remain for more than 4 days [24,30,31] .
Antibiotic lock prophylaxis is to wash the catheter lumen with antibiotic solutions and then release the antibiotic into the catheter lumen. Vancomycin and ciprofloxacin were used for this purpose. Routine use of vancomycin cannot be recommended since vancomycin may cause a risk of enterococcal resistant infections [30] .
Indications for Catheter Removal
In cases where catheter-related infection is considered but there is no redness, tenderness, purulent discharge at the catheter insertion site, the catheter should be removed and cultured from the tip. A new catheter is inserted from the same place via the guide wire. If culture is negative, the catheter is left in place, if culture positivity is present, the catheter should be removed and a new catheter inserted from a different area. Indications for catheter removal as a result of catheter infection are given in Table 4 and cases where they can be left in place are given in Table 5 [1,3-6,8-11] .
As a result; appropriate catheter and catheter placement, aseptic catheter placement, proper catheter care, replacement of the catheter if necessary, avoidance of antibiotic prophylaxis are the basic rules that must be followed in preventing catheter infections.
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