HAIs: thinking beyond the hospital door

Albert Alexander, a 43-year-old British policeman, was the first person to be treated with penicillin. For five days, he improved dramatically. However, despite reusing penicillin extracted from his urine, supplies ran out, he relapsed and died from Staphylococcus aureus septicaemia.1, 2 Before penicillin around 20% of people who contracted pneumococcal pneumonia died. Mortality with pneumococcal bacteraemia reached 50%, and 80% to 100% from pneumococcal meningitis.3 Since the 1940s penicillin has saved countless lives. However, researchers rapidly realised that some staphylococci strains were naturally resistant to penicillin. Alexander Fleming isolated penicillin from a naturally occurring mould and, not surprisingly, staphylococci evolved protective mechanisms. In 1960, methicillin – which is resistant to staphylococcal betalactamase (the enzyme responsible for penicillin resistance) – reached the clinic. Initially, all S. aureus strains succumbed to methicillin, but UK microbiologists reported the first isolate of methicillinresistant S. aureus (MRSA) within a year of its introduction. The acronym remains, despite methicillin’s demotion from the antimicrobial armamentarium.4 Today, MRSA remains a pervasive clinical problem. However, since 1990, products containing octenidine have helped to tackle this and to prevent other hospital-acquired infections (HAIs) and improve wound care. In the UK today, octenidine, an effective and well-tolerated broad-spectrum antimicrobial, is available in a variety of formats including gel, irrigation solutions and body washes. MRSA and other HAIs impose major clinical and economic burdens on the NHS. In the EU, MRSA results in an estimated one million extra days of hospitalisation at an attributable cost of ?380 million in hospitals each year.5 The Department of Health’s Quick guide to health and care reform notes that “poor quality care” such as iatrogenic infections or preventable falls “can cost the NHS billions of pounds every year”. Nevertheless, improving infection control does not alter fixed healthcare costs. However, effective and efficient infection control releases capacity, which the hospital can redeploy to treat new patients, improve productivity and enhance the quality of care.5 Such redeployment could help the NHS bridge the current “productivity gap”. The Nuffield Trust estimates that providers need to make 4% efficiency savings, while experiencing a 1.5% cut to the tariff.6 Furthermore, litigation can prove expensive: a UK MRSA case resulted in an out-of-court settlement of around £400,000.5 Against this background, concerted infection control initiatives reduced the number of MRSA bacteraemias in England by 52% between January and March 2009, and January and March 2011. Similarly, the number of Clostridium difficile infections declined by 65% between the 2007/8 quarterly average and January to March 2011. Nevertheless, English Trusts reported 334 and 4827 cases of MRSA bacteraemia and C. difficile infection respectively between January and March 2011. Moreover, the Health Protection Agency notes that the growth in multiresistant Escherichia coli strains “continues to cause concern.”7 Clearly, the NHS needs to maintain effective infection control, especially in the face of new threats. Microbiologists, for example, have been expressing increasing concern about strains of S. aureus that produce a toxin called Panton-Valentine leukocidin (PVL), which causes leukocyte destruction and tissue necrosis. Indeed, PVL+ S. aureus is highly pathogenic and an important cause of necrotising pneumonia, sepsis as well as severe skin and soft tissue infections.8 PVL+ S. aureus appears to be relatively common, although most strains remain methicillin-sensitive. A study from a London hospital reported that 9.7% of clinical isolates and 20.8% of skin and soft tissue specimens contained S. aureus expressing PVL genes. PVL+ MRSA accounted for 0.8% of isolates. However, microbiologists found PVL+ methicillinsensitive S. aureus (MSSA) in 9.0% of specimens. PVL+ strains were three times more frequent in males and 3.7 times more common in those aged 20 to 39 years. Furthermore, 71.1% of PVL+ S. aureus infections originated in the community.8 Meanwhile, researchers from Southampton analysed 59 S. aureus isolates, 13 of which were community acquired. More than half (54%) of community-acquired strains were MRSA and, of these, 43% expressed PVL. However, the absolute figures were small – three cases of PVL+ MRSA and five cases of PVL+ MSSA.9 Most skin and soft tissue infections caused by PVL+ S. aureus do not require hospital admission.8 Nevertheless, the higher rate of infection in skin and soft tissue specimens emphases the importance of effective wound care to tackle this reservoir of infection. Moreover, PVL+ S. aureus underscores that highly pathogenic bacteria lurk in the community. Colonising strains can act as reservoirs that emerge as overt clinical infections or that spread to other patients.10

Decolonisation

Indeed, increasing evidence suggests that effective infection control means thinking beyond the hospital door. Microbiologists identified community-acquired (CA; community-associated) MRSA in the mid-1990s. Initially, reports of CA-MRSA came from specific groups, such as close communities (e.g. military recruits and sports teams), men who have sex with men, district nurses, injecting drug users and the homeless.11 Today, CA-MRSA’s epidemiological characteristics are reminiscent of CA-MSSA. For instance, CA-MRSA is increasingly common in healthcare settings, including causing infections with an onset more than 72 hours after hospital admission. In the USA, mathematical modelling predicts that CA-MRSA will become the dominant MRSA strain in hospitals and healthcare facilities.11 Increasing MRSA transmission from colonised livestock, particularly pigs, to, for example, farm and abattoir workers and veterinarians exacerbates the problem.4 Indeed, approximately 20% and 60% of people show persistent and intermittent S. aureus colonisation respectively.12 Colonisation often precedes bacteraemia.12 In one study of S. aureus bacteraemia, 82% of patients had blood isolates identical to those from their anterior nares. In another study, 1% of patients with nasal S. aureus colonisation subsequently developed bacteraemia between 1 day and 14 months after microbiologists took the nasal sample. In 86% of cases, the S. aureus blood isolates were identical to nasal samples.10 As these studies imply, colonised inpatients could import pathogens, such as MRSA and PVL+ S. aureus, from the community. For example, colonisation of the insertion site by the patient’s skin flora is the most important route through which central venous catheter insertion sites become infected. (The other main routes are microorganisms transmitted from healthcare workers and catheter hub contamination).13 Decolonisation therefore reduces the risk that community-acquired bacteria will result in HAI. Octenidine (0.2-1.6%) washes can reduce levels of resident skin bacteria by 90.00% to 99.98%, depending on the concentration and number of applications.14 In a clinical trial, 45 hospitalised MRSA carriers were decontaminated using intra-nasal mupirocin combined with Octenisan body wash (an octenidine-based antimicrobial hair and body wash). After the first 5-day wash cycle, MRSA was no longer detectable in 69% of patients. Eight of the 14 patients who remained MRSA-positive after the first cycle underwent a second cycle with an eradication rate of 50%. According to an internal study by Octenisan manufacturer, Schülke, overall, the regimen eradicated MRSA in 78% of carriers. Rohr et al15 decolonised MRSA using intranasal mupirocin combined with an octenidine body wash in 32 hospitalised carriers for five days. The overall decolonisation rate for all sites (nose, forehead, neck, axilla and groin) was 64% seven to nine days after the procedure. Octenidine’s broad spectrum of action also means that the wash lotion is able to eradicate a range of potential pathogens including multiresistant strains, Gram-positive and Gram-negative bacteria and fungi. Indeed, skin’s resident flora consists of more than 200 species of bacteria and a few eukaryotic fungi. Octenidine is not absorbed through intact or broken skin and retains a residual, detectable effect 24 hours after application. Doctors, nurses and pharmacists could recommend that patients use an octenidine-based skin wash for five days before or during a stay in hospital.