◆ Many patients in the intensive care unit (ICU) suffer from one or several device-related health care-associated infections (HAI).
◆ Intrinsic factors such as age, immunosuppression, neutropenia, or multi-organ failure are preconditions for HAI, but the main risk comes from breaches in aseptic technique of using medical devices.
◆ Emerging resistance due to the use of broad-spectrum antibiotics and poor infection control is a major challenge in the treatment of device-related HAI.
◆ Device-related HAI are preventable, but implementation of best practice in infection control is not easy.
◆ Successful prevention programmes offer a comprehensive protocol; follow a multidisciplinary approach in preparation, and a multimodal training and education programme in implementation.
Many patients in the intensive care unit (ICU) suffer from one or several device-related health care associated infections (HAI) during their stay, including central line-associated bloodstream infections (CLABSI), ventilator-associated pneumonia (VAP), and catheter-associated urinary tract infection (CAUTI). Such infections are related to the use of medical devices, such as central lines, intratracheal tubes, and urinary catheters. Utilization ratios expressed as device-days per hospital-days can be up to 70, 50, and 80% for central lines, ventilators, and urinary catheters, respectively. Although factors on the patient side, such as immunosuppression, neutropenia, age, or multi-organ failure are important preconditions, device-related factors such as dwell-time or breaches in aseptic technique are the predominant risk factors for HAIs in the ICU. Shortcomings in structure and organization, such as low nurse-to-patient ratio, high bed-occupancy, or high ratios of float and pool nurses interfere with the use of medical devices and, thus, are equally important [1,2,3].
Catheter-associated bloodstream infections
Almost half of all positive blood cultures obtained in a hospital are due to nosocomial BSI. Of these, most are primary and associated with central catheters. CLABSI represent 10–15% of all HAIs in intensive care  and the incidence density is two to seven episodes per 1000 catheter-days, depending on ward type, institution, and geographical region. CLABSIs are associated with increased length of stay (7–20 days), additional costs (US$ 3,000–40,000), and an attributable mortality of 2–12% .
In most institutions, a shift in predominant organisms from Gram-negative bacilli to Gram-positive cocci has been observed over the past two decades. However, in countries with limited resources, Gram-negative pathogens and, among these, non-fermentative organisms such as Pseudomonas species and Acinetobacter species are predominant. The shift towards Gram-positive cocci observed in high-resource countries is largely due to the use of intravascular devices and the fact that the proportion of patients with risk factors, such as neutropenia, solid organ and bone marrow transplantation, or the use of immunosuppressive agents has increased. Coagulase-negative Staphylococci (CoNS) are the most common pathogens isolated from blood cultures. Often considered as contaminants, their detection may not always be harmless and an associated mortality up to 18% has been reported. However, mortality from CoNS is usually much lower, while mortality from Staphylococcus aureus can be as high as 25%. Detection of S. aureus on a catheter tip is a predictor for subsequent bacteraemia, even in the absence of clinical signs and negative blood cultures at the time of catheter removal. The proportion of Candida species has considerably increased in many institutions, mainly due to prolonged treatments with multiple and broad-spectrum antibiotics and the use of total parenteral nutrition. CLABSI due to Candida species has a poor prognosis with an attributable mortality between 15 and 55%, especially when antifungal treatment is delayed by 3 or more days. An important shift in the epidemiology has occurred over the past decades with decreasing infections due to C. albicans, but increasing infections due to non-albicans isolates, particularly C. glabrata. The latter represents an important problem as this species is often resistant to azoles.
CLABSI is diagnosed by combining clinical signs, such as fever or systemic inflammatory response syndrome (SIRS), with microbiological cultures. If the central line is the most probable source of infection, it should be removed and the tip cultured. Detection of identical species with the same susceptibility testing confirms the catheter as a source. Alternatively, blood can be obtained from the catheter and from a peripheral vein. If the growth time of the blood sampling from the catheter is shorter than the growth time of the blood sampling from the peripheral vein by two hours or more, the central line is the most likely source for the bloodstream infection . This test is called differential time to positivity and has the advantage that the catheter can be left in place.
The management of suspected CLABSI in the ICU combines early antimicrobial treatment and the active search for sources other than the catheter. The choice of antibiotics must include at least a substance active against Gram-positive and non-fermentative micro-organisms, taking into account the local susceptibility pattern of bacteria and whether the patient was transferred from a country with a high prevalence of resistance. Immunocompromised or neutropenic patients should receive also an antifungal agent active against Candida species. Immediate effective treatment is important as either delayed or inappropriate antibiotic treatment is associated with increased morbidity and mortality. A multidisciplinary approach with close collaboration between the physician in charge of the patient, the infectious disease specialist, and the microbiology laboratory, improves the accuracy of the empiric therapy. Once susceptibility testing from micro-organisms identified from blood cultures is available, antibiotic treatment should be adjusted accordingly. Procalcitonin-based de-escalation of antibiotic therapy can be helpful to reduce antibiotic use. If CLABSI is confirmed, the central line should be removed and a new catheter inserted at a different site. Guide-wire exchange is a risk for recurrent BSI and should be avoided. Recent data suggest that an antibiotic lock in addition to a systemic antibiotic therapy can be used as a salvage strategy in long-term catheters if signs of exit site or tunnel infection are absent and blood cultures reveal the presence of CoNS or enterococci. Removal is mandatory in severe or complicated infections, in the presence of shock, recurrent BSI, and when S. aureus, Gram-negative bacilli, or Candida species are isolated. Relapse, continuous fever, or bacteraemia despite catheter removal requires active search for complications, such as endocarditis, metastatic abscess, or septic thrombophlebitis.
CLABSI prevention programmes must focus on best practice with evidence-based guidelines on catheter insertion and catheter care. The strategy should be multidisciplinary and multimodal to encourage adoption and implementation [7-9]. Further, reduction can be achieved by using chlorhexidine-impregnated dressings, catheters coated with chlorhexidine/silver sulfadiazine or antibiotics, or by daily bathing the patients with chlorhexidine . Lock-solutions with taurolidine, citrate, ethylenediaminetetraacetic acid (EDTA), or ethanol reduce catheter colonization, but still have to prove their efficacy in CLABSI reduction under routine working conditions.
VAP is the most frequent nosocomial infection in critical care, contributing between 30 and 50% to the total number of HAIs. Published VAP rates range widely from 2.5 to 35.7 episodes per 1000 ventilator-days due to case-mix variations, inconsistent use of diagnostic tools, varying definitions, and different reporting modalities. VAP is associated with attributable costs of US$10,000–25,000, which is mainly due to an excess length of stay by 5 to 7 days. Attributable mortality is estimated at about 10–30% . It is particularly high in VAP due to S. aureus and is associated with severe sepsis.
The most common pathogen is S. aureus, followed by P. aeruginosa, Haemophilus influenzae, Klebsiella species, Streptococcus pneumoniae, and Escherichia coli. Early onset VAP is due more often to S. pneumoniae and H. influenzae, while late onset VAP is due mainly to S. aureus (including meticillin-resistant S. aureus (MRSA)) and non-fermentative bacteria, such as P. aeruginosa.
The diagnosis of VAP relies on clinical signs, such as fever, onset of purulent secretions, or worsening gas exchange in combination with radiological findings, such as infiltrates, consolidates, or cavitations. Positive blood cultures, if not related to another infection, contribute to the diagnosis. The addition of quantitative culture samples obtained by bronchoscopic techniques improves diagnostic accuracy by reducing the number of VAP diagnoses by 30% to 50%.
Given the high risk of mortality, early and appropriate, broad-spectrum antibiotic therapy should be prescribed with adequate doses to optimize antimicrobial efficacy. An empiric therapy regimen should be installed, including agents from different antibiotic classes than the patient has recently received. VAP due to P. aeruginosa should be treated with a beta-lactam antibiotic in combination with an aminoglycoside. Linezolid is an alternative to vancomycin in the treatment of VAP due to MRSA. Infections due to carbapenem-resistant Gram-negative micro-organisms should be treated with a regimen including colistin. De-escalation of antibiotics should be considered once susceptibility data are available. If lower respiratory tract cultures are negative and the patient has improved clinically after 72 hours, antibiotics may be stopped at that time. A treatment duration of 8 days is recommended for patients with uncomplicated VAP who have received an appropriate therapy initially with a good clinical response and with no evidence of infection due to non-fermenting Gram-negative bacilli .
◆ Hand hygiene, preferably using alcohol-based hand rub.
◆ Glove and gown use for endotracheal tube manipulation.
◆ Backrest elevation to 30–45°.
◆ Maintenance of tracheal cuff pressure of 20 cmH2O.
◆ Use of orogastric tubes.
◆ Gastric overdistension avoidance.
◆ Good oral care with chlorhexidine.
◆ Elimination of non-essential tracheal suctioning.
Good compliance with such techniques has been shown to reduce VAP-rates by 50% . There is evidence that subglottic secretion drainage is effective in VAP prevention.
Catheter-associated urinary tract infection
Similar to non-ICU settings, Enterobacteriaceae (E. coli, Klebsiella species, Proteus species, Enterobacter species, Citrobacter species, Providencia species, Serratia species, Morganella species) are the predominant pathogens in CAUTI. However, non-fermentative micro-organisms, such as Pseudomonas species, Acinetobacter baumannii, and Stenotrophomonas species are also isolated. Gram-positive bacteria, such as Enterococcus species and S. aureus are less frequently identified.
The definition of CAUTI in the ICU is controversial and challenging as clinical signs such as urgency, frequency, dysuria, or suprapubic tenderness cannot be assessed in sedated patients. The only clinically useful sign is fever. In practice, CAUTI diagnosis is likely if the patient has a fever without apparent source and confirmed by a positive urine culture (≥105 micro-organisms per cm3 of urine with no more than two species of micro-organisms).
CAUTI treatment must take into account antibiotic susceptibility testing from identified micro-organisms. Pre-emptive therapy of ICU-acquired CAUTI must include an antibiotic with activity against Enterobacteriaceae and non-fermentative micro-organisms. Emerging resistance in Gram-negative bacteria is a real concern. Enterobacteriaceae, in most countries harbour extended-spectrum beta-lactamases, in particular Klebsiella species and E. coli, and carbapenem resistance is emerging worldwide.
Most guidelines recommend limiting catheter use by evaluating the necessity of catheterization and reviewing the ongoing need for urinary catheters. Catheter insertion should use an aseptic technique with sterile equipment. Whether silver alloy or antibiotic-impregnated catheters reduce the risk of infection remains a controversial issue. However, there is consensus to use the smallest bore catheter. For catheter maintenance, a closed drainage system should be used, routine irrigation should be avoided, and the drainage bag must be placed below the level of the bladder. Routine urine cultures must be avoided as asymptomatic bacteriuria should not be treated. Systemic antibiotic prophylaxis is not recommended outside urinary tract malformations in small children .
Implementation of best practice
The successful implementation of best infection control practices is not an easy task. It depends on individuals, the hospital setting, the local and national context, the design of the prevention programme and how it is structured and conducted . Successful prevention programmes offer a comprehensive protocol; follow a multidisciplinary approach in the preparation phase, and a multimodal training and education strategy in the implementation phase . Education and training sessions should be as practical as possible and actively involve frontline workers, e.g. in workshops, simulator training, and focus groups . Distributing guidelines or merely promoting bundles is insufficient to motivate health care workers to change practice . Messages must be embedded in a multimodal training strategy and actively supported by the top leaders . Champions who actively lead efforts to implement best practices in their teams and a positive organisational culture by fostering working relationships and communication across units and staff groups help in the implementation process. Surveillance of process indicators or outcomes, such as CLABSI, VAP, or CAUTI, preferably in a surveillance network similar to US National Healthcare Safety Network, the German nosocomial infection surveillance system (KISS), or the International Nosocomial Infection Control Consortium (INICC), and in combination with timely performance feedback to health care workers at the frontline help to maintain best practice.
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