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Volume 3 No 26; 3 July 2009

Treatment approach announced for pandemic flu

The Government announced, on 2 July, an end to the containment phase in the management of the current pandemic flu outbreak in the UK [1].

The announcement was made as further clusters were identified around the country where there is good evidence of significant levels of transmission of swine flu within the community. As a result, public health interventions to reduce spread were deemed no longer appropriate and the focus has moved to the treatment of individual patients with antivirals.

The move to using antivirals for treatment only is consistent with the approach being taken in other countries across the world including the USA, Canada, Australia, New Zealand, Chile, Mexico and elsewhere.

Since the first cases were seen in the UK the policy has been to contain the spread of the virus using various public health interventions including giving antivirals to those who were symptomatic (as a treatment) as well as to their close contacts (to prevent them from developing the disease). This was successful in containing the spread but could not have been sustained indefinitely.

Diagnosis of cases will henceforth be on the basis of clinical observation rather than laboratory testing. Those who have flu-like symptoms will be assessed by a doctor and if diagnosed with swine flu will be given antivirals to manage their illness. Routine swabbing of suspected cases will cease (although a proportion of patients will be tested for surveillance purposes) and the Health Protection Agency will no longer trace close contacts or provide antivirals to limit spread.

Treatment

All those who have contracted swine flu will continue to be offered antiviral drugs and doctors have been advised to give priority to early treatment with antivirals of people in higher risk groups: this includes those with long-term lung, kidney, neurological, liver or heart disease; children under five; people over 65; those with diabetes mellitus; the immunosuppressed (whether caused by disease or treatment); patients who have had drug treatment for asthma within the past three years; and pregnant women.

The Chief Medical Officer for England has written to healthcare professionals with the latest information and guidance [2].

Development of existing influenza surveillance systems

The Health Protection Agency's role will continue to be to provide scientific advice to Government and to use the established surveillance systems to monitor the spread and incidence of the disease.

HPA has internationally respected surveillance systems for monitoring incidence and assessing the impact of flu, which it has operated through the normal "flu season" over the last few years. These systems have effectively informed policy and planning, and evaluation of interventions (particularly the uptake of seasonal flu vaccine), and have been identified in pandemic preparedness plans as central to surveillance activities in the pandemic situation.

These systems will, however, be augmented by additional surveillance activities that are relevant to the pandemic situation, eg continuing assessment of the severity of disease associated with this novel virus, and monitoring for changes in the characteristics of the virus.

References

1. "Treatment approach announced for pandemic flu", (HPA press release of 2 July 2009). HPA website: National Press Releases.

2. Department of Health. "New H1N1v influenza: current situation and next steps", 2 July 2009.

Multi-resistant hospital bacteria linked to India and Pakistan

A National Resistance Alert, issued in January 2009 [1], warned of an increasing number of carbapenem-resistant strains of Enterobacteriaceae being identified in UK hospital patients, a significant proportion of whom had received medical treatment abroad.

Three categories of carbapenem-destroying enzymes ("carbapenemases") were recognised among submissions during 2008 and deemed to be of potential major public health concern by the HPA Centre for Infection's Antibiotic Resistance Monitoring and Reference Laboratory (ARMRL): (i) metallo-beta-lactamases [2, 3]; (ii) KPC enzymes [2, 4 ] and (iii) OXA-48 enzyme, prevalent among K. pneumoniae in Turkey [5]. The metallo enzymes were "VIM" types, often linked to patients previously hospitalised in countries of the Eastern Mediterranean.

It has now become clear that a further metallo-beta-lactamase type - designated NDM-1 ("New Delhi Metallo-1") - is swiftly emerging. Four isolates producing this enzyme have been recognised among submissions from 2008, with 18 more so far in 2009. The total of 22 bacteria with NDM-1 enzyme represent the largest single group of carbapenemase producers referred to ARMRL and comprise K. pneumoniae (14), Escherichia coli (4), Citrobacter freundii (2), Enterobacter cloacae (1) and Morganella morganii (1) from 19 patients at 17 hospitals. Typing by the HPA's Laboratory for Healthcare Associated infections shows that they are clonally diverse, with no outbreaks and only one instance of possible transmission between two patients.

Critically, at least 9/19 affected patients have had recent hospitalisation in India or Pakistan. Similarly, the patient from whom the first NDM-1 enzyme producer was described - in Sweden in 2008 - had prior medical contact in India [6]. One UK patient, who developed a bloodstream infection with an E. coli that produced NDM-1 enzyme had received treatment for a haematological malignancy in both India and the UK; two others had undergone cosmetic surgery in India and one of these presented to a UK hospital with a wound infection that grew a mixed microbial flora including K. pneumoniae with NDM-1 enzyme; others had received renal or liver transplantation in Pakistan.

Epidemiological data for NDM-1 enzyme within India are limited and anecdotal, but ARMRL has reports of the enzyme from isolates from multiple cities, with a sharp rise in carbapenem resistance in Delhi since 2006 (whether due to NDM enzyme or not). E. coli with NDM-1 enzyme have also been also found by a collaborator in Karachi, Pakistan. Carbapenems are widely available in the Indian subcontinent, are widely used owing to prevalent cephalosporin resistance, and have doubtless exerted selection pressure.

ARMRL data suggest that isolates with NDM-1 enzyme have been repeatedly imported to the UK from the Indian subcontinent, though there may now also be UK circulation since some affected patients have no immediately identifiable overseas links.  This situation resembles that with producers of VIM and KPC carbapenemases where we have seen multiple importations via patients previously hospitalised in Greece, Cyprus and Israel along with locally acquired infections. However the population flow between the UK and the Indian subcontinent is larger with some elective medical tourism as well as some patients who, for family reasons, divide treatment between the UK and India or Pakistan.

Carbapenems are the only antibiotics reliably active against many otherwise multi-resistant gram-negative opportunist bacteria, particularly those with extended-spectrum beta-lactamases (ESBLs) [7, 8]. The growing emergence and diversity of carbapenemase producing strains is therefore a major concern.

Treatment presents major challenges. Most isolates with NDM-1 enzyme are resistant to all standard intravenous antibiotics for treatment of severe infections. Polymyxin is usually active in vitro (though not vs. M. morganii, an intrinsically resistant species) but of uncertain clinical efficacy, especially in pneumonia, owing to poor lung penetration. Tigecycline is often active in vitro, but has low serum levels, is unsuitable for urinary infections and, more generally, is of unproven efficacy in severe infections. ARMRL is urgently reviewing the activity of both developmental and old, otherwise abandoned, antibiotics against producers.

ARMRL therefore urges hospitals to be vigilant to multi-resistant gram-negative bacteria in patients with recent hospital contact in the Indian subcontinent as well as the Eastern Mediterranean. If Enterobacteriaceae are found resistant to any carbapenem they should be sent to ARMRL for investigation [9]. Great care should be taken to prevent onward transmission of producers. Comprehensive infection control advice can be provided by the HPA's Laboratory of Healthcare-Associated Infection [10] but key aspects include isolation of sources and screening of cases and close hospital contacts for gut carriage.

References

1. HPA. National Resistance Alert: carbapenemases in Enterobacteriaceae. Health Protection Report [serial online] 2009; 3(4): news. Available at: http://www.hpa.org.uk/hpr/archives/2009/news0409.htm#enterora.

2. Nordmann P, Cuzon G, Naas T. The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. Lancet Infect Dis 2009; 9: 228-36.

3. Vatopoulos A. High rates of metallo-beta-lactamase-producing Klebsiella pneumoniae in Greece - a review of the current evidence. Euro Surveill 2008; 13.

4 . Pournaras S, Protonotariou E, Voulgari E, Kristo I, Dimitroulia E, Vitti D, et al. Clonal spread of KPC-2 carbapenemase-producing Klebsiella pneumoniae strains in Greece. J Antimicrob Chemother. 2009 ePub Jun 13.

5. Carrer A, Poirel L, Eraksoy H et al. Spread of OXA-48-positive carbapenem-resistant Klebsiella pneumoniae isolates in Istanbul, Turkey. Antimicrob Agents Chemother 2008; 52: 2950-4.

6. Yong D, Giske CG, Toleman M et al. A novel subgroup metallo-beta-lactamase (MBL), NDM-1. 48th Annual ICAAC/IDSA 46th Annual Meeting, Washington DC, October 25-28, 2008 2009; C1-105: 87.

7. Pitout JD, Laupland KB. Extended-spectrum beta-lactamase-producing Enterobacteriaceae: an emerging public-health concern. Lancet Infect Dis 2008; 8: 159-66.

8. Zahar JR, Lortholary O, Martin C et al. Addressing the challenge of extended-spectrum beta-lactamases. Curr Opin Investig Drugs 2009; 10: 172-80.

9. ARMRL director: Dr David Livermore: david.livermore@hpa.org.uk.

10. LHCAI director: Professor Barry Cookson:barry.cookson@hpa.org.uk

Salmonella and E. coli bacteria found in packets of shelled nuts

A recent study carried out by the Health Protection Agency and the Local Authorities Co-ordinators of Regulatory Services (LACORS) has revealed the presence of salmonella and E. coli bacteria in a small number of samples of ready-to-eat shelled nuts.

Consumption of shelled nuts (kernels) has increased, reflecting a growing preference for snacks that are both healthy and convenient. The study was undertaken to explore the microbiological safety of a selection of these products including brazil nuts, cashews and peanuts amongst others.

Between October 2008 and March 2009, councils collected 2,866 samples of nut kernels of different varieties were collected from randomly selected retail premises such as supermarkets and health food shops. Testing of the kernels showed that at least 99% were of a satisfactory or acceptable quality in microbiological terms. However, 0.1% of samples were found to be unsafe due to the presence of salmonella, which is unacceptable in ready-to-eat foods. E. coli , the presence of which indicates poor hygiene, was found in a total of 0.8% of the samples; and in 0.03% of samples the level of E. coli was assessed as being too high and therefore unsatisfactory in microbiological terms.

Reference

1. HPA/LACORS. Assessment of the microbiological safety of edible nut kernels on retail sale in the UK with a focus on Salmonella spp. Downloadable from the HPA website at Food Sampling.