Nosocomial antimicrobial resistance surveillance

Journal of Hospital Infection (I 999) 43 (Supplement):

Nosocomial surveillance

M

S97-S IO3

antimicrobial

resistance

B. D. Cooltson Laboratory of Hospital Infection, Central Public Health Laboratory, PHLS, 6 I Colindale Avenue, London NW9 5l-U

The global threat of antimicrobial resistance and potentially Summary: is a serious matter under review currently by the WHO and many countries I consider the optimal surveillance scheme and point out the various biases have been using in the UK over the last decade. MRSA are used as an trends have been identified in these systems and the information has, once 0 1999 value to the MRSA control working party. Keywords:

Surveillance;

antimicrobial

resistance; antibiotic

The global threat of antimicrobial resistance and potentially untreatable infections is reflected in the number of presentations on various aspects of this problem at this Conference. A recent WHO’ report outlined measures to control the problem, emphasizing the importance of multidisciplinary approaches and that infection control and antibiotic prescribing control were our two major weapons in this battle. Their relative roles have yet to be established, but probably vary with the antimicrobial agent and type of resistance. I describe here the requirements of, and problems with, nosocomial antibiotic resistance surveillance systems and a number of strategies and collaborations in which the Laboratory of Hospital Infection (LHI) has been involved over the last few years.

Requirements

of a surveillance

system

In a stimulating leader, Gaynes2 reminded us of the importance of learning to live with the biases in antibiotic-resistance data and that a

0 195-670

I /99/OSOO97 + 07 $12.00/O

resistance; MRSA;

untreatable infections throughout the world. in the systems that we example where similar again, proved to be of The Hospital

infection

Infection

Society

control.

good surveillance system does not guarantee you will make the right decisions, but reduces the chances of making the wrong ones. Such a surveillance system must be designed to ensure that infection control teams (ICTs) remain motivated and continue to send appropriate data for central analysis. Variation in the ICTs contribution to the surveillance system creates problems with data interpretation over time and is a particularly important example of ‘sample migration’. Many others will be apparent in this paper. It is essential that timely and appropriate analyses are fed-back to ICTs addressing agreed questions and that appropriate denominator information has been included to enable stratification and comparisons of local data with the total aggregated data. It is also important to preserve the confidentiality of ICTs’ data and to be particularly aware of the possibilities of deductive disclosure. Antibiotic resistance data enable the design of local empirical therapy and antibiotic policy

0 I999 The Hospital

Infection

Society

S98

8. D. Cookson

and informs costing studies of antibiotic prescribing. It also has educational and audit potential and enables the prioritization of research funding. Other uses of the data e.g., for commercial purposes, should have been discussed fully with all contributors. Methodology should be as simple as possible, using standardized or comparable surveillance and susceptibility testing methods with periodic validation. Surveillance data should ideally be interpreted with prescription data and consideration given to interaction with other infection control/patient care parameters. Surveillance and audit cycles should also be interactive and enable the continuous improvement in patient care and the control of antibiotic resistance and the infections they cause. Increasingly in today’s health service, surveillance will also have to show costeffectiveness and be sufficiently adaptable to interact with research project data and any reasonable local requirements.

Variables affecting surveillance

antibiotic

resistance

There are many local laboratory variables that need to be considered by the centre by analysing data from these laboratories. There is considerable variation in the type and number of antibiotics tested from laboratory to laboratory. This is well illustrated in the Laboratory of Hospital Infection (LHI) ICT mupirocin resistance questionnaire survey where, although 90.5% of laboratories tested for mupirocin resistance, less than half used a method that would detect high level resistance.3 In addition, although 20 (12%) of 168 laboratories tested all isolates, most (85%) focused on methicillin resistant Staphylococcus aweus (MRSA), 66% when therapy was indicated on the request form and 25% on S. aweus from certain sites. Our recent Clinical Audit project4 emphasized the importance of the correct collection of clininterpreting the relevance of ical specimens, coagulase negative staphylococci was problematic and some of the centres should review their methods of specimen collection e.g., for intravenous-lines. Another problem was the

paucity and variation in the collection of clinical specimens from infected patients: 21% of patients with supposed urinary tract infections did not have specimens sent for analysis, although there were huge ranges from O-100% in different specialties even in the same hospital. The situation was far worse for patients with lower respiratory tract infections, where two thirds did not have specimens sent, even where there was sputum production noted in the surveillance record. This increased to 89% where the record indicated ‘no increase in sputum’ or ‘no sputum’, an interesting example of how infection surveillance data can help interpret data for local audit. The ever-decreasing lengths of hospital stay are resulting in fewer specimens being taken and infections manifesting only after discharge. This is threatening the effectiveness of our alert organism surveillance system’ and altering the denominators of antibiotic resistance surveillance. Standardized post-discharge surveillance methods are being explored in other studies we are performing. Our Clinical Audit project4 also found that many infections were being diagnosed just before discharge and that duration of antibiotic therapy could not be audited because of lack of discharge prescription data. Another problem is our inability accurately to identify the organisms in which antibiotic resistance is emerging. Thus, in our Clinical Audit project4 ‘coliforms’ were identified in 70% of urinary tract infections (UTIs) and 20% of lower respiratory tract infections (LRTIs). There is a need to negotiate improvements in bacterial identification for specific periods or for agreed antibiotic resistances or high-risk areas of the hospital, such as intensive care units. The costs and benefits of this additional work must also be considered. Probably one of the most difficult problems of all is the lack of agreement as to what clinical, demographic and epidemiological information should accompany clinical and screening specimens, and even whether to record the latter two sources separately or in a single database. This will eventually be made easier with the development of interactive computerized information systems.6 Management will increasingly require

Nosocomial

antimicrobial

resistance

surveillance

these data which, if they are to be used to monitor quality of clinical care, will need to include details of MRSA patients who acquired their organisms in other hospitals or from previous admissions, a level of sophistication that many have yet to achieve.7 Finally, there is the variability in the quality of the antimicrobial susceptibility testing pev se. The methods in the UK vary enormously and there is an urgent need to improve these as well as the quality assurance assessments. We have distributed via the NEQAS UK system isolates with various resistance mechanisms. The results in some areas show improvements. Thus the detection of high-level (VunA phenotype) vancomycin resistance in enterococci was identified accurately in 96 and 99% of UK laboratories in 1993 and 1995 respectively, whilst only 50% could correctly detect low-level resistance (Vu&?) in 1993 increasing to 60% in 1994 and J Snell, personal com70% in 1995 (Mr munication). A 1995 LHI ICT questionnaire probably provides a reason for this continuing problem, in that one third of 113 responders still only used 30 pg vancomycin discs rather than the 5 pg discs recommended for susceptibility testing. The introduction of local quality assurance groups to discuss NEQAS results in the UK may be a way forward. This will be attempted in our DG-XII funded project (HARMONY).

Sources of antibiotic resistance surveillance information with varying degrees of bias We have used a variety of sources of data to monitor the emergence and dynamics of microbial antibiotic resistance. These all have biases and I will largely discuss the trends for MRSA. Isolates submitted to the Reference Laboratory for typing or antimicrobial susceptibility testing

Isolates sent to the LHI for typing or susceptibility testing are subject to many biases and currently lack denominator information. It

s99

is apparent from the patterns of referral that certain hospitals send many isolates to us and we are informed that they are performing useful local surveillance. These centres could perform the kernel of a sentinel laboratory surveillance system, although this is being explored with the British Society of Antimicrobial Chemotherapy at present. The antibiotic susceptibility testing data from referred isolates enables interpretation of national trends in antibiotic surveillance data.‘jz8 It also provides a tentative typing system for ICTs. We have written criteria for referral of staphylococcal isolates to the LHI, which encourage ICTs to use the antibiograms to assist selection of isolates and to examine the ways they use our typing service. The criteria have been modified recently and piloted, but ICTs varied in their preferences for the old, the new and their own criteria (often with good reason) and we will need to develop a consensus. New request forms are also being piloted. These currently require data on the numbers of outbreak patient isolates and the nature of infection or colonisation and will interact with regional surveillance in a combined central database. My goal is to develop a unified isolate recording system that will provide ICTs with their local data and derive subsets of these data for central typing referrals and surveillance information. The LHI staphylococcal workloads have increased from - 12,000 in 1990 (N 50% MRSA) to 43,000 in 1997-98 (~85% MRSA). The reasons for this include the emergence of new ‘supra-regional’ epidemic strains (EMRSA-15 and 16) that have a particular propensity for spread. This has been further encouraged by changes in health care delivery e.g., increasing inter-ward transfers,4’9 decreasing lengths of hospital stay reducing the effectiveness of alert organism surveillance.5 In addition, MRSAs are now referred to us from newly affected parts of the country without local PHLS typing facilities, such as the West Midlands and East Anglia. To inform the newly convened MRSA working party6 and confirm that the trends from the reference isolates were correct, we distributed an MRSA ICT questionnaire in 1 994-95.r0 This confirmed the predominance of EMRSA-16 (27% of all outbreaks) in the South-East of the

SIOO

Table

B. D. Cookson

I

ICT Questionnaire results: Average number of outbreaks per /CT and MRSA type

Region Thames West Midlands East Anglia Oxford Wales South Western Yorkshire Northern

EMRSA-I6 4.37 0.3 4.8 4.0 0 0.3 0.2 0

EMRSA- I5

EMRSA-3

0.6 15.7 I.6 I.3 I .25 0.2 I.7 0. I

I.1 0.1 0 0 0 0 0 0

country and that of EMRSA-15 (24%) in the West Midlands but, as we realised, there were also many outbreaks (~40%) with other MRSAs. ICTs should also consider local behaviour of such strains, as we had pointed out in the previous guidelines and not rely purely on National EMRSA status. The invasiveness of MRSA was confirmed as well as the intraregional variations in outbreak numbers (Table I), disease and carriage. The latter, of course, also depends on the intensivity of screening. The invasiveness was in part due to the units affected with 7% on intensive care units, 2% special care baby units, 18% surgical, 19% medical, 13% orthopaedic and 19% on acute elderly care wards. However, 10% occurred on long stay elderly care wards, an important reservoir for the acute wards and there was a surprising amount of data on the situation in elderly care/ nursing homes. Forty-two ICTs were aware of 394 homes with MRSA in all Regions, 62 homes had been screened by 27 ICTs and spread was detected in 45 (72%) homes. Various MRSAs were implicated and 143/749 (19%) patients were positive, although there were large ranges. A mupirocin resistance questionnaire3 was also distributed that confirmed the emerging problem with mupirocin resistance that we had detected in the reference 1aboratory.l’ Interpretation of the data was difficult in view of the susceptibility testing problems mentioned above. However, it provided important insights into the perceived nature of the problem3 and the alternative topical decontamination methods being used (38% used a variety of topical disinfectants such as chlorhexidine, triclosan and

between~onuoryI994 and July I995 Other 0.8 0.3 3.4 3.0 I .4 3.2 I .o 0.8

All 6.8 16.3 9.8 8.3 2.7 3.7 2.9 0.9

povidone iodine, 18% neomycin/chlorhexidine, 8% colistin/bacitracin, 7% fusidic acid, and 1% chloramphenicol). Continuous Surveillance Antibiotic Resistance (CSAR) in bacteraemia and meningitis isolates to the Communicable Diseases Surveillance Centre (C/XC) LHI The CDSC/LHI blood stream infection (BSI) reporting system has shown a dramatic increase in the MRSA proportion of S. UUY~US bacteraemias8’12 (MRSA/SA%) and these are reflected in the increase in incidents of MRSA typed by the reference laboratory between 1989-98 (Figure 1). However, there is another interesting trend in this and referred isolate datasets. Earlier in the decade, as also reflected in the 1995 ICT questionnaire, EMRSA-16 and 15 predominated in the South-East and West Midlands respectively, in the last two years there is evidence of a more even spread of the problem (Table II). There has also been a marked increase in the bacteraemia data, thus the MRSA/SA% has increased between 1995 and 1997 from 2.5 to 18.4% in the North, 2.3 to 36.5% in the North-West and from 5-32.9% in the Wessex Regions. The ICT questionnaire data showed a very significant relationship between colonization and invasive disease. EMRSA-16 has two super-antigens6 (enterotoxin-A and TSST-1) and is capable of invasive disease13 and EMRSA-16 toxic shock isolates have been referred to us, albeit in small numbers, over the last few months. It will be important to monitor

Nosocomial

antimicrobial

resistance

35 L 30

SIOI

surveillance

the 1993-94 National Prevalence survey, MRSA colonization was the major risk factor for hospital acquired infection.14 Some of the interim results are shown in Table III. Data are from a widely distributed sample around the country and have not been stratified by region. If one presumes that prevalence is approximately twice incidence, then the MRSA/ SA% for BSIs is very comparable to that of the CDSC/LHI system at that time. The clinical audit project performed two years later showed a 24% MRSA/SA BSI%, again in agreement with the CDSC/LHI BSI data. Urinary tract infection MRSA/SAO/ data were 26%, pneumonias 37% and other LRTIs 54%. The 19 hospitals were evenly distributed throughout England and Wales, although only some of the hospitals were affected by MRSA at that time. Much higher rates were thus evident in certain hospitals. The increasing incidence of MRSA infections is seen in even more recent data from the newly established English Nosocomial Infection National Surveillance Scheme (NINSS). Infection control teams receive their own confidential data. Aggregated data (February to September 1997 shown with permission of the NINSS team) showed that MRSA were the commonest cause of surgical site infection and comprised 61% of all such S. aureu~ infections. In the bacteraemia module (first three months data for 733 bacteraemias), MRSA was the fourth commonest organism (coagulase-negative staphylococci 24.7%, Eschevichia coli 12.5%, methicillin-sensitive S. aweus 11.8% and MRSA 7.8%) and comprised 40% of all S. aureu~ bacteraemias.

317

r

t

25 20 t 15 10 c

n

1993 1995 1997 1992 1994 1996

1989 1991 1993 1995 1997 1990 1992 1994 1996

% MRSA/SA

Outbreaks

BSIs

typed100

Figure I Blood-stream infections reported to CDSClLHl and Incidents of MRSA typed between 1989 and 1997.

Table II MRSA incidents sent for typing to LHI between july I997 and July 1998” Region

EMRSA-3

EMRSA-I 5

EMRSA- I6

I7 0 0 0 0 I 0

249 66 73 I IO I30 143 63

310 12 31 I I8 51 62 85

ThameslSouth East West Midlands Trent AnglialOxford North/Yorkshire North-West South-West * Preliminary

data provided

the bacteraemia EMRSA strains Nosocomial

by Dr Judith Richardson.

and toxic shock data as the spread and evolve.

infection

suweillance

data

Several such studies have informed the surveillance of antimicrobial resistance and I will again use MRSA to illustrate this point. In

Table

Ill

Interim H/SIICNA/PHLS

/993-94

Prevalence Survey Data

Category

BSI

SSI

IV-lines

LRTI

Bone

MRSA no. MSSA no. %M RSAISA %MRSA/AII infections

4 26 I3 3

I3 73 I5 3

3 II 21 5

I3 22 37 6

I IO 9 3

MSSA, Methicillin-sensitive S. oureus; BSI, blood stream infection; IN lines, intravenous lines.

SSI, surgical site infection;

LRTI, Lower respiratory

All 92 239 28% 6.6% tract infection;

s102

Comments on other antibiotic-resistant organisms and strategic considerations Isolates referred to LHI show other worrying trends, notably the emergence of glycopeptideresistant enterococci (GRE)” some of which have epidemic potential.” The re-emergence of epidemic strains of Klebsiella is another cause for concern.17 Our typing data now include typing information on the resistance gene elements.18-20 This work is showing that either the rate of multiplication of these elements differs from that of the chromosomal DNA, or that the genes are being acquired by the same strains from different sources.3 Expensive genetic typing tools need to be evaluated with ICTs on wellcollected strains. Only in this way will we be able to unravel the dynamics of the various antimicrobial resistance problems and focus our various preventative or intervention strategies. HARMONY will help establish such collections as it explores the feasibility of conducting an ecological study of the incidence of antimicrobial resistance in relation to infection control and prescribing practices as well as of staff/ patient ratios and intensivity of care on intensive care units in several countries. Finally, there is the possibility of sentinel surveillance. Such laboratories could also act as pioneers for improving the quality assurance of antimicrobial susceptibility testing. Specific problems would then be targeted for e.g., periodic ‘occurrence’ surveillance studies in PHLS and or NHS laboratories linking with typing information.21 The latter is expensive and has to be carefully planned. Comprehensive surveillance would currently be an expensive solution but as information technology improves and becomes cheaper, the ideal may be achieved. Others have pointed out that pneumococcal antibiotic resistance can vary even within a city, ” and the same has always been true for the prevalence of MRSA.23 Surveillance has been described as information for action and we must not lose sight of the need for local action on this information. Our two major weapons, infection control and antibiotic prescribing control, must be sharpened continuously.

B. D. Cookson

Acknowledgements The views stated here are those of the author. I would like to thank the following who contributed in so many ways to this paper: Hazel Aucken, Alan Johnson, Polly Kauffman, David Livermore, Richard Marples, Donald Morrison, Ty Pitt, Judith Richardson, Neil Woodford.

References 1. Abou

2.

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YZ, Acar JF, Ayliffe GAG et al. Report of the World Health Scientific Working Group on monitoring and management of bacterial resistance to antimicrobial agents. WHO, Geneva, Switzerland, 1995:W’HO/CDS/BVI/95.7. Gaynes R. Surveillance of antibiotic resistance: learning to live with bias. Infect Control Hosp Epidemiol 1995; 16: 623-626. Cookson BD. The emergence of mupirocin resistance: a challenge to infection control and antibiotic prescribing practice. J Antimicrob Chemothev 1998; 41: 11-18. Glynn A, Ward V, Wilson J, Charlett A, Cookson BD, Taylor L, Cole N. Hospital-acquiyed infection: Surveillance, policies and practice. London: PHLS, 1997. ISBN 0 901144 40 1. Rahman A, Mackenzie D, Marples R, Cookson BD. Identification of MRSA incidents in hospitals. r Hosp If 1995; 30: 76-78. Ayliffe GAJ, Casewell MSC, Cookson BD et al. Revised guidelines for the control of methicillinresistant Staphylococcus aweus infections in hospitals. Report of a combined working party of the British Society of Antimicrobial Chemotherapy, the Hospital Infection Society and the Infection Control Nurses’ Association. J Hosp Infect 1998; 39: 253-290. Cookson BD, Webster M, Burnett J, Butler EA, Wright DA. A hospital computer system as a tool for infection control. In: Bryant J, Roberts J, Windsor P, eds. Current perspectives in health caye computing. Weybridge, Surrey: British J Health Care Computing Ltd. 1986; 126-131. Speller DCE, Johnson AP, James D, Marples RR, Charlett A, George RC. Resistance to methicillin and other antibiotics in isolates of Staphylococcus aweus from blood and cerebrospinal fluid, England and Wales, 1989-95. Lancet 1997;350: 323-325.

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