Hospital-acquired infections (HAIs) remain a significant cause of morbidity and mortality in the UK. A 1-day prevalence study of European ICUs found that 21% of patients had an ICU-acquired infection. Patients in an ICU setting are more susceptible to HAIs due to underlying illness severity, presence of prosthetic material, e.g. central lines, urinary catheters, and exposure to broad-spectrum antibiotics. The risk of HAIs in ICU patients can be reduced by adherence to basic infection control precautions, prudent antimicrobial prescribing, and care of invasive devices.
Infection control precautions
Standard infection control precautions (SICPs)
SICPs are necessary to reduce the risk of transmission of micro-organisms and should be carried out as a minimum for all patients. They include:
• Hand hygiene
• Use of personal protective equipment (PPE), e.g. gloves, aprons
• Control of the environment
• Management of equipment
• Occupational exposure management
• Management of blood and body fluid spillages
• Appropriate patient placement
• Safe disposal of waste and linen.
Transmission-based precautions (TBPs)
TBPs should be used in addition to standard precautions when a patient is known or suspected to have a specific infection. TBPs will be based on the mode of transmission of the particular agent and can be divided into three main categories:
• Droplet, e.g. influenza, meningococcal disease
• Contact, e.g. Clostridium difficile, meticillin-resistant Staphylococcus aureus (MRSA)
• Airborne, e.g. Mycobacterium tuberculosis, chickenpox.
Not all three categories will necessarily be essential for each particular infectious agent and advice should therefore be sought from local infection control teams.
Scrupulous hand hygiene is considered the single most effective measure for the prevention of healthcare-associated infection. Audits of hand hygiene opportunities, however, often reveal poor compliance amongst healthcare workers.
Skin flora can be divided into two types:
• Transient organisms—these are picked up from the patient or environment and are not usually part of the normal flora, e.g. MRSA, Pseudomonas spp.
• Resident organisms—these are organisms such as coagulase-negative staphylococci and Corynebacterium spp., i.e. skin flora which are found deep in the dermis and don't tend to cause infection unless introduced during an invasive procedure, e.g. central line insertion.
In addition to the five key moments in Box 31.1, hand washing should take place after handling food, using the toilet, and when visibly contaminated.
Alcohol hand gel
Alcohol hand gel can be used between episodes of single patient care (hygienic hand disinfection). When hands are visibly contaminated soap and water should be used (hygienic hand wash). Alcohol gel is not sufficient for hand hygiene in patients with Clostridium difficile as it has no activity against spores.
Prudent antimicrobial prescribing
All trusts will have antimicrobial management teams who are responsible for the development, implementation, and audit of antibiotic policies. Policies will generally be available for empirical prescribing, surgical prophylaxis, and for organism-specific conditions. Other methods employed to control antibiotic prescribing include:
• Alert antibiotic policies, i.e. antibiotics that can only be prescribed after discussions with a microbiologist or infectious diseases physician.
• IV to oral switch policies.
• Electronic prescribing.
• Automatic stop orders.
• Antibiotic cycling or rotation.
The aim of such interventions is the reduction of antibiotic resistance and the reduction of infections due to resistant organisms such as Clostridium difficile and MRSA amongst others.
Clostridium difficile infection (CDI)
Clostridium difficile is an anaerobic Gram-positive rod which was first linked to pseudomembranous colitis in 1978. It is now the most common cause of hospital-acquired diarrhoea and is associated with ↑ morbidity and mortality. In 2008, a new ribotype was recognized following an outbreak in Quebec, Canada. This 027 strain now present in the UK is associated with more severe disease, disease refractory to treatment, and mortality, effects which are due to hyper-production of toxin. Risk factors for CDI in the ICU patient include the use of broad-spectrum antibiotics, proton pump inhibitors (PPIs), prolonged duration of stay, and serious underlying illness.
Reducing the risk of CDI
• Hand hygiene—hands must be washed with soap and water according to the five moments listed in Box 31.1.
• Isolation—patients should be nursed in a single room.
• Use of PPE, e.g. gloves, aprons.
• Enhanced cleaning—the environment should be cleaned twice daily with a chlorine-based detergent.
• Prudent prescribing—prescribe as per local policy. Review need for antibiotics daily. Restrict use of high-risk antibiotics—the 4Cs—Clindamycin, Co-amoxiclav, Cephalosporins, Ciprofloxacin.
• Review need for PPI.
Management of CDI
• Consider stopping antibiotics, PPIs, antimotility agents.
• Implement stool chart—monitor frequency daily.
• Review fluid and electrolytes daily.
• Assess severity of disease. Severity criteria include: colonic dilatation >6cm, creatinine >1.5× baseline, temperature >38.5°C, white cell count >15×109 cells/L, immunosuppression:
• Patients with 0–1 severity markers and non-severe disease should be treated first line with metronidazole 400mg three times a day for 10–14 days.
• Patients with >2 severity markers should be commenced on oral vancomycin 125mg four times a day for 10–14 days. If ileus is present IV metronidazole should be added.
• If abdomen is distended or painful a radiological assessment should be undertaken and a surgical review requested.
MRSA remains an important nosocomial pathogen and a cause of significant morbidity and mortality in an ICU setting. Cardiothoracic patients will normally undergo preoperative MRSA screening of two or more body sites. Ideally those who test positive should undergo decolonization and have two negative MRSA screens prior to surgery.
Decolonization therapy consists of:
• Nasal application of 2% mupirocin ointment three times daily for 5 days.
• Body washes with agents such as HiBiSCRUB® or Clinisan Advance™.
In an emergency situation where there is no time for eradication, a decolonization regimen should be commenced as soon as possible and surgical antibiotic prophylaxis should consist of antibiotics with activity against MRSA, e.g. glycopeptide ± gentamicin.
Influenza is one of the commonest causes of upper respiratory tract infection. Respiratory complications such as viral and bacterial pneumonias are more common in patients with pre-existing heart and lung disease.
In the critical care setting infection control precautions (ICPs) for patients during an influenza pandemic should be implemented on admission and continued for the duration of the illness. These ICPs and other containment measures include:
• Adherence to SICPs and droplet precautions.
• Isolation or cohorting of affected patients.
• Hand hygiene.
• PPE—in addition to gloves and aprons, surgical masks are recommended for close contact (<1m) with a patient. An FFP3 respirator and eye protection are recommended in patients undergoing aerosol generating procedures.
• Exclusion of symptomatic staff and visitors.
• Environmental cleaning.
• Vaccination of patients and staff.
In addition, there are specific precautions which should be taken in relation to respiratory equipment. These include:
• The use of disposable equipment where possible.
• Closed ventilation systems where possible.
• The ventilatory circuit should not be broken unless essential—if a break occurs appropriate PPE for aerosol-generating procedures should be worn.
• All respiratory equipment should have a high efficiency bacterial/viral filter which should be changed in line with manufacturers’ recommendations.
Care of devices
Devices such as urinary catheters and peripheral and central venous catheters are associated with an ↑ risk of HAI. In intensive care settings care bundles have been implemented to reduce the number of device-associated HAIs. These bundles are comprised of basic evidence-based procedures grouped together in a single protocol with the aim being to improve patient outcomes. Bundles can be performed during insertion and maintenance of the device. An example of a peripheral venous catheter bundle is as follows;
• Check the PVCs in situ are still required.
• Remove PVCs where there is extravasation or inflammation.
• Check PVC dressings are intact.
• Consider removal of PVCs in situ >72 hours.
• Perform hand hygiene before and after all PVC procedures.
Coia JE, Duckworth GJ, Edwards DI, Farrington M, Fry C, Humphreys H, et al. Guidelines for the control and prevention of MRSA in healthcare facilities. J Hosp Infect. 2006;63:S1–S44Find this resource:
Department of Health. Pandemic Influenza. Guidance for Infection Control in Clinical Care. London: Department of health; 2008. Available at: <http://www.dhsspsni.gov.uk/guidance_for_infection_control_in_critical_care__420kb_.pdf>.Find this resource:
Health Protection Scotland. PVC Care Bundle. Available at: <http://www.hps.scot.nhs.uk/haiic/ic/PVCCareBundle.aspx>.
Vincent JL, Bihari DJ, Suter PM, Bruining HA, White J, Nicolas-Chanoin MH, et al. The prevalence of nosocomial infection in intensive care units in Europe. Results of the European Prevalence of Infection in Intensive Care (EPIC) study. JAMA 1995;274:639–44.Find this resource:
World Health Organization. WHO Guidelines on Hand Hygiene in Healthcare. 2009. Available at: <http://www.who.int/rpc/guidelines/9789241597906/en/>.
Empiric broad-spectrum antimicrobial therapy is started when there is a strong clinical suspicion of infection. This should be de-escalated to narrow-spectrum antimicrobial therapy if culture results permit to reduce the risk of resistant organisms and opportunistic infections, e.g. Clostridium difficile.
• Blood cultures from intravascular catheters and a peripheral vein
• Pus samples (better than swabs at identifying organisms)
• Wound swabs
• Sputum or tracheal aspirates
• Urine and faeces.
• All members contain a β-lactam ring structure
• Mode of action is to inhibit cell wall synthesis
• Classification system:
Allergy and side effects
• Allergic reactions:
• Anaphylaxis to penicillin (Type I, IgE-mediated reaction) presents with pruritus, flushing, urticaria, angioedema, and hypotension but is rare (1–4/10,000 administrations). All β-lactam antibiotics should be avoided in these patients.
• Serum sickness—late reaction with fever, rash, adenopathy, and arthritis.
• 2% of patients with true penicillin allergy (positive skin test) will react after cephalosporin administration. 1% of patients with true penicillin allergy will react to a carbapenem.
• Dermatological—skin rash, usually maculopapular or morbilliform starting within 2 weeks of starting antibiotic seen in 1–5% of exposed patients.
• Diarrhoea, C. difficile infection (as with any antibiotic).
• Cholestatic jaundice—usually flucloxacillin and β-lactamase-resistant penicillins. Ceftriaxone can cause biliary sludging.
• Interstitial nephritis, glomerulonephritis.
• Central nervous system:
• Encephalopathy with high-dose treatment, seizures.
• Haemolytic anaemia, thrombocytopaenia, neutropenia.
• Benzylpenicillin (also known as Pen G)
• Orally absorbed penicillins (e.g. Pen V)
• Antistaphylococcal penicillins (e.g. meticillin, flucloxacillin)
• Extended-spectrum penicillins (e.g. amoxicillin)
• β-lactamase-resistant penicillins (e.g. co-amoxiclav, piperacillin/tazobactam)
• Benzylpenicillin is used to treat infections due to Streptococcus pyogenes (e.g. cellulitis, necrotizing fasciitis), Streptococcus agalactiae and Streptococcus pneumoniae (if susceptible to penicillin).
• Penicillin V is used for mild infections due to these agents, primarily pharyngitis (‘Strep throat’) and for S. pneumoniae prophylaxis in asplenic patients.
• Flucloxacillin is the standard antibiotic therapy for meticillin-sensitive Staphylococcus aureus (MSSA) infections, as well as empirical therapy for skin and soft tissue infections.
• Amoxicillin is used to treat infections caused by most enterococci and some susceptible Gram-negative organisms such as Escherichia coli. Due to advantages in oral absorption over penicillin V, amoxicillin is often used to treat community-acquired pneumonia in order to target S. pneumoniae which is the most common cause.
• β-lactamase-resistant penicillins are used to target organisms that produce β-lactamase enzymes which destroy the β-lactam ring of Pen V, Pen G and amoxicillin. Co-amoxiclav is a combination of clavulanic acid, which is a potent inhibitor of many β-lactamases and amoxicillin. Co-amoxiclav is often used to treat HAIs such as pneumonia where resistance is often more of an issue. Tazobactam is similar in potency to clavulanic acid, but when combined with piperacillin (Tazocin®), results in broad-spectrum Gram-positive and Gram-negative activity including against Pseudomonas aeruginosa.
• 1st generation—usually used for treatment of simple urinary tract infection, e.g. cephalexin.
• 2nd generation—enhanced Gram-negative activity, e.g. cefuroxime.
• 3rd generation—further enhancement of Gram-negative cover, e.g. cefotaxime, ceftriaxone, and ceftazidime (active against P. aeruginosa).
• 4th generation—improved spectrum of activity including P. aeruginosa, e.g. cefepime.
• 5th generation—new agents as yet not widely available, e.g. ceftobiprole with activity against MRSA.
• Cefuroxime is still used as part of surgical prophylaxis in some hospitals, although there is a drive to change this to flucloxacillin ±gentamicin.
• Ceftriaxone is still the preferred agent in the treatment of bacterial meningitis; however, it is also being used as part of outpatient antibiotic therapy (OPAT) services.
• Ceftazidime is an effective agent for treatment of P. aeruginosa infections.
• Broad-spectrum antibiotics with activity against Gram-positive, Gram-negative, and anaerobic bacteria.
• Imipenem—first licensed carbapenem, although associated with CNS toxicity.
• Ertapenem—once-daily carbapenem with no activity against P. aeruginosa but active against other Gram-negative organisms and anaerobes.
• Meropenem—activity against P. aeruginosa and the most commonly used carbapenem, with approval to treat CNS infection as well.
Vancomycin and teicoplanin inhibit cell wall synthesis and are bactericidal against most Gram-positive bacteria:
• Glycopeptides are not absorbed when given orally, therefore they must be given by IV infusion for all suspected or proven infections apart from CDI.
• Continuous ambulatory peritoneal dialysis peritonitis
• Catheter-related bloodstream infection
• Oral vancomycin is the second-line treatment for CDI that is not responding to metronidazole.
• Are more common with vancomycin than with teicoplanin.
• Red man syndrome—infusion-related histamine-mediated flushing during or immediately following rapid infusion.
• 5–15% develop a decline in renal function; monitor drug levels.
• 20–30% of patients develop nephrotoxicity when vancomycin is given with an aminoglycoside such as gentamicin.
• Ototoxicity is rare.
• Gentamicin is the most commonly used aminoglycoside in UK, with others, such as amikacin and tobramycin, reserved for specific situations or in the treatment of gentamicin-resistant organisms.
• Aminoglycosides inhibit bacterial protein synthesis and are bactericidal against Gram-negative and some Gram-positive organisms.
• Clinical uses:
• Surgical prophylaxis in combination with a β-lactam or glycopeptide antibiotic.
• Empirical therapy of severe infections such as complicated urinary sepsis, intra-abdominal sepsis, and neutropenic sepsis often in combination with other agents.
• Targeted therapy against numerous Gram-negative organisms such as E. coli and P. aeruginosa, as well as in combination with a β-lactam or glycopeptide antibiotic in order to treat staphylococcal or streptococcal infection.
• Topical gentamicin used in treatment of eye and ear infections. Aerosolized tobramycin used in CF patients.
Allergy and side effects
• Nephrotoxicity—incidence estimated at 10–20%, although toxicity is reversible.
• Ototoxicity may result in vestibular or cochlear damage which may lead to irreversible hearing loss.
• Neuromuscular blockade—aminoglycosides contraindicated in myasthenia gravis.
• If patients need to continue therapy beyond 48 hours, trough drug levels should be monitored.
• Quinolones inhibit bacterial nucleic acid synthesis and are bactericidal against both Gram-positive and Gram-negative organisms.
• Ciprofloxacin is the most commonly used quinolone in UK, and has potent Gram-negative activity, including P. aeruginosa and some activity against staphylococci but little activity against Streptococcus pneumoniae. Ciprofloxacin also has some activity against Legionella pneumophila, Mycoplasma pneumoniae and Chlamydophila pneumoniae.
• Norfloxacin and ofloxacin have a similar antimicrobial spectrum to ciprofloxacin.
• Moxifloxacin and levofloxacin have Gram-negative coverage similar to that of ciprofloxacin; however, they are less active against P. aeruginosa. Both moxifloxacin and levofloxacin are more active against S. pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydophila pneumoniae when compared to ciprofloxacin.
• Extensive, especially in patients with true penicillin allergy.
• Ofloxacin is used in treatment of prostatitis, gonorrhoeae, and pelvic inflammatory disease.
• Levofloxacin and moxifloxacin are used second-line for treatment of community-acquired pneumonia, as well as in the treatment of tuberculosis.
Allergy and side effects
• GI symptoms are most common and quinolones have been implicated in several C. difficile outbreaks worldwide.
• CNS symptoms such as headache and dizziness have been reported in up to 11% of patients. Quinolones may induce seizures in patients with epilepsy and should be avoided.
• Rash occurs in 0.4–2.2% of patients.
• Tendon rupture has been reported in adults.
• Arthropathy was seen in juvenile animal studies but has yet to be seen in humans.
• QT prolongation has been observed, especially with newer agents.
• Erythromycin and clarithromycin have similar antimicrobial spectrum as penicillin and are commonly used in patients labelled penicillin allergic. They are active against some staphylococci, specifically MSSA, and most streptococci. They are also active against the agents causing atypical pneumonia, namely Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydophila pneumoniae.
• Azithromycin has greater Gram-negative activity than erythromycin and can be given as a single dose to treat chlamydial infections.
• Used to treat community-acquired pneumonia, usually in combination with a β-lactam.
• Also used to treat severe campylobacter gastroenteritis.
• Clarithromycin used in Helicobacter pylori eradication.
Fishman NO. Antimicrobial management and cost containment. In Mandell GE, Bennet JE, Dolin R (eds), Principles and Practice of Infectious Diseases (5th edn, pp. 539–46). London: Churchill Livingstone; 2000.Find this resource:
Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, et al. EPIC II Group: International study of the prevalence and outcomes of infection in intensive care units. JAMA 2009;302(21):2323–9.Find this resource: