Conceived and designed the experiments: SW DW. Analyzed the data: DC TP SW. Wrote the paper: SW DW. Other: Critically reviewed the manuscript: LO DC TP.
The authors have declared that no competing interests exist.
Despite a substantial burden of non-bacteraemic methicillin resistant
We used microbiology and patient administration system data from an Oxford hospital to estimate monthly rates of first nosocomial MRSA bacteraemia, and nosocomial MRSA isolation from blood/respiratory/sterile site specimens (“sterile sites”) or all clinical samples (screens excluded) in all patients admitted from the community for at least 2 days between April 1998 and June 2006. During this period there were 441 nosocomial MRSA bacteraemias, 1464 MRSA isolations from sterile sites, and 3450 isolations from clinical specimens (8% blood, 15% sterile site, 10% respiratory, 59% surface swabs, 8% urine) in over 2.6 million patient-days. The ratio of bacteraemias to sterile site and all clinical isolations was similar over this period (around 3 and 8-fold lower respectively), during which rates of nosocomial MRSA bacteraemia increased by 27% per year to July 2003 before decreasing by 18% per year thereafter (heterogeneity p<0.001). Trends in sterile site and all clinical isolations were similar. Notably, a change in rate of all clinical MRSA isolations in December 2002 could first be detected with conventional statistical significance by August 2003 (p = 0.03). In contrast, when monitoring MRSA bacteraemia, identification of probable changes in trend took longer, first achieving p<0.05 in July 2004.
MRSA isolation from all sites of suspected infection, including bacteraemic and non-bacteraemic isolation, is a potential new surveillance method for MRSA control. It occurs about 8 times more frequently than bacteraemia, allowing robust statistical determination of changing rates over substantially shorter times or smaller areas than using bacteraemia as an outcome.
Nosocomial isolation of MRSA from sites other than blood is also of clinical significance, and can arise in two settings: one in which the patient is clinically infected, and the other in which they are not and are carriers of the organism. Carriage of
Here, we describe nosocomial MRSA bacteraemia and isolations from other clinical samples in a large teaching hospital over a 10 year period, demonstrating that changes over time are very similar, but that non-bacteraemic isolations are about 8 times more common. We further investigate whether, using MRSA isolation from all sites of suspected infection as a surveillance measure, more rapid and precise estimates of trends in nosocomial MRSA isolation can be formed than by the use of bacteraemic isolates alone.
Our study included data from the John Radcliffe Hospital, the Radcliffe Infirmary, the Churchill Hospital and the Horton General Hospital (the Oxford Radcliffe Trust, ORH, UK), which offer the majority of specialist regional services plus acute clinical and bacteriology services to about 600,000 people. Admissions to other much smaller hospitals in the area (including a specialist orthopaedic hospital, psychiatric hospitals, and several community hospitals) were not included. Microbiological processing used standard techniques, as recommended by the standard operating procedures of the Health Protection Agency. Patient admissions, excluding outpatients, between 1 January 1997 (1 January 1999 for Horton) and 31 July 2006 were anonymously linked to information on microbiology isolates from 1 January 1995 and 31 July 2006, using previously described methods
The outcomes considered were
nosocomial isolations of MRSA
blood cultures
blood cultures and all other samples taken due to clinical suspicion of infection (non-screening “clinical samples”), except for vascular line tip cultures, which we excluded because of their relationship to blood cultures.
blood cultures and clinical samples only from respiratory and normally sterile sites taken under aseptic technique, such ascites, joint aspirates, cerebrospinal fluid, pre-prosthetic material, and collections of pus.
Following the principle that an outcome should be counted if either the event of interest or a more serious event has occurred, we compared MRSA isolation from blood cultures with isolation from both blood cultures
For blood, blood/respiratory/sterile site and all clinical isolates, we analysed those samples:
taken during the period 1 April 1998 and 30 June 2006
when there was no positive MRSA isolation from that group of sites within the previous 14 days, analogous to the process recommended for bacteraemia reporting
which were the first such positive isolation per admission, to focus on new infections rather than repeat isolations which could be influenced by persistent, unresolved infected sites (such as fistulae and wound drains).
We excluded the following admissions from analysis:
those with MRSA isolated from the group of sites within the first 2 days of admission, since we wished to study nosocomial isolation
inter-hospital transfers, since their total prior hospital stay was unknown.
We used Poisson regression to estimate the incidence of nosocomial MRSA infection, including as denominator one day for every part of a calendar day spent in ORH hospitals >2 days after admission (providing the patient had not had an outcome within 2 days of this admission) up to the earliest of discharge, death or the MRSA outcome; and numerator whether or not MRSA was isolated from a sample taken on that day for each patient. Patients could contribute more than one nosocomial isolation to analysis if these occurred in different admissions. A succession of simple two trend models were fitted to explore changes in rate over calendar time, and the model minimising the Akaike Information Criterion (AIC
Not required as linkage was anonymous; approval for the study obtained from the Caldicott guardian as with our previous studies.
Repeated isolation of MRSA from different clinical samples from a single patient is common; to estimate the number of infections, we determined the first clinical isolation (FCI) of MRSA for each patient admitted between 1 April 1998 and 1 July 2006, initially considering all clinical samples (excluding screens). 8% of FCIs >2 days after admission were from blood, with 15% from other normally sterile locations (including pus and periprosthetic samples), 10% from respiratory samples, 59% from surface cultures (e.g. ulcers and wounds), and the remaining 8% from urine specimens, a total of 3450 FCIs (
Bacteraemia N = 441 | Blood, respiratory, sterile site N = 1464 | All clinical isolates N = 3450 | Global | (1) vs (2) | (1) vs (3) | (2) vs (3) | ||
Factor | Subcategory | n (%) or median (IQR) | n (%) or median (IQR) | n (%) or median (IQR) | p | p | p | p |
blood | 441 (100%) | 346 (24%) | 269 (8%) | - | - | - | - | |
sterile site | 729 (50%) | 527 (15%) | ||||||
respiratory | 389 (27%) | 352 (10%) | ||||||
surface/genital swab | 2031 (59%) | |||||||
urine | 271 (8%) | |||||||
1998 | 20 (5%) | 91 (6%) | 204 (6%) | 0.05 | 0.68 | 0.14 | 0.04 | |
1999 | 32 (8%) | 115 (8%) | 248 (7%) | |||||
2000 | 44 (10%) | 153 (11%) | 365 (11%) | |||||
2001 | 54 (13%) | 196 (14%) | 401 (12%) | |||||
2002 | 74 (18%) | 248 (17%) | 523 (16%) | |||||
2003 | 92 (22%) | 258 (18%) | 587 (18%) | |||||
2004 | 59 (14%) | 187 (13%) | 526 (16%) | |||||
2005 | 45 (11%) | 170 (12%) | 489 (15%) | |||||
2006 | 21 | 46 | 107 | |||||
16 (7–31) | 14 (7–28) | 15 (8–30) | 0.04 | 0.07 | 0.67 | 0.02 | ||
female | 167 (38%) | 569 (39%) | 1471 (43%) | 0.02 | 0.71 | 0.06 | 0.01 | |
(years) | 73 (63–81) | 72 (58–80) | 74 (60–82) | 0.0003 | 0.05 | 0.59 | 0.0001 | |
screening or clinical sample | 55 (12%) | 275 (19%) | 684 (20%) | 0.001 | 0.002 | <0.0001 | 0.40 | |
120 (27%) | 401 (27%) | 861 (25%) | 0.16 | 0.94 | 0.30 | 0.07 | ||
56 (15–290) | 59 (17–272) | 69 (18–314) | 0.22 | 0.66 | 0.20 | 0.16 | ||
2 (0–4) | 2 (0–4) | 2 (1–4) | 0.04 | 0.62 | 0.06 | 0.04 | ||
10 (0–33) | 11 (0–37) | 13 (1–41) | 0.02 | 0.37 | 0.03 | 0.04 | ||
trauma/A&E/ortho/cardio | 34 (8%) | 172 (12%) | 352 (10%) | 0.002 | 0.004 | 0.006 | 0.05 | |
specialityobs/gynae/paeds/ENT | 16 (4%) | 88 (6%) | 219 (6%) | |||||
haemat/onc/nephr | 29 (7%) | 50 (3%) | 145 (4%) | |||||
surgery | 162 (37%) | 511 (35%) | 1086 (31%) | |||||
medicine: elective | 5 (1%) | 20 (1%) | 55 (2%) | |||||
medicine: emergency | 195 (44%) | 623 (43%) | 1593 (46%) | |||||
145 (33%) | 489 (33%) | 1043 (30%) | 0.07 | 0.84 | 0.25 | 0.03 |
univariable p values from chi-squared or Kruskal-Wallis/ranksum tests for categorical and continuous variables respectively.
first MRSA isolation from specified samples this admission (predominant site according to order above when MRSA isolated from multiple types of specimens on the same day).
3 months April to June 2006: percentages are of complete financial years only.
any sample tested at ORH from 1 January 1995 onwards, during or outside of an ORH admission, but strictly before the current admission
Note:excluding repeated positive isolations within a single admission.
Notably, the characteristics of patients with bacteraemia, blood/respiratory/sterile site and any clinical MRSA isolation had many similarities (
TOP PANELS: Monthly nosocomial MRSA incidence, and change in relative rates from blood cultures, the combination of bacteraemia, respiratory and sterile site samples, and all clinical samples. MIDDLE PANELS: estimates of relative annual rate of increase or decrease in incidence, calculated each month from April 2000 to June 2006. LOWER PANELS: the point at which changes in rate were most likely to have occurred, and when they could have been confidently detected by an infection control team monitoring trends.
Poisson regression was used to assess the significance of these trends. We found that incidence of nosocomial MRSA bacteraemia increased by 27% per year to July 2003 (p<0.001,
Bacteraemia | Blood, respiratory, sterile site | All clinical isolates | |
Positive isolations | 441 | 1464 | 3450 |
- mean isolations per month in 1999 | 2.3 | 9.4 | 19.4 |
- mean isolations per month in 2002 | 5.8 | 20.8 | 42.7 |
- mean isolations per month in 2005 | 3.5 | 13.2 | 40.6 |
Patient days at risk from >2 days after admission to the earliest of discharge, death or MRSA isolation | 2,676,180 | 2,654,119 | 2,617,870 |
Most likely time that trend in rates changes (“changepoint”) | July 2003 | November 2002 | December 2002 |
Fold change in isolation rate per year to this changepoint (HR (95% CI) p) | 1.27 (1.18–1.37)<0.001 | 1.25 (1.19–1.31)<0.001 | 1.23 (1.19–1.27)<0.001 |
Fold change in isolation rate per year subsequently (HR (95% CI) p) | 0.82 (0.72–0.93) 0.002 | 0.87 (0.82–0.92)<0.001 | 0.95 (0.92–0.98) 0.008 |
Range of times of rate trend change which cannot be distinguished statistically from this changepoint | March 2002 to January 2004 (22 months) | June 2002 to April 2003 (10 months) | September 2002 to July 2003 (10 months) |
First month after April 2000 when data up to and including this month suggest a date in this range is the most likely time for a change in rate trend with p<0.05 | July 2004 | October 2003 | August 2003 |
identified as per Methods (see
based on difference in AIC of <3.84 from the best-fitting changepoint model.
Given recent intensive infection control initiatives, a key question is when the increase in MRSA incidence actually reversed. Studying our hospital Trust from 1998–2006, the most likely time that the reduction in MRSA incidence started varied a little with outcome (July 2003, November 2002 and December 2002 respectively), but the range of times that could not be distinguished statistically from this most likely time overlapped substantially (
Continuous review and monthly reporting of MRSA bacteraemia is a mandatory requirement in the UK. We considered to what extent the three MRSA outcome measures described above (bacteraemia, isolation from blood/respiratory/sterile sites, and all clinical isolates) could help an infection control team decide whether and how MRSA incidence was changing, by plotting for data up to and including each month from April 2000 through June 2006, the best current estimate of the relative annual rate of increase/decrease in MRSA incidence classified by the statistical evidence for this having changed (
Oxford Radcliffe Trust is one of the largest Acute Hospital Trusts in the UK. An average Acute Hospital Trust is about half the size, and a small Trust on the 25th centile of the UK distribution is about 35% the size
Durations of two equal periods required to detect a 25% (left panel) or 50% (right panel) reduction in rate of MRSA isolation, for a variety of sizes of hospital unit.
Here we show that whilst trends over time in nosocomial bacteraemic and non-bacteraemic isolates of MRSA are similar in a large UK Acute Hospital Trust over a 10 year period, non-bacteraemic clinical isolates are about 8-fold more frequent, with their ratio relatively constant. For reasons which are not investigated here, incidence of both outcomes declined progressively from early 2003, offering the opportunity to assess the ability of isolations from different types of clinical specimen to monitor changes in MRSA. Similar patient characteristics and time trends suggest that similar populations are likely to be at risk for both bacteraemic and non-bacteraemic isolation, with bacteraemia an indicator of the most severe infection across a spectrum rather than having different epidemiology. Indeed, there is extensive overlap between these groups, with two thirds of patients with bacteraemia also having MRSA isolated from a non-blood source during the same admission, around half of these isolations being prior to the bacteraemia (rather than prompted by a positive blood culture). Due to the vastly different incidence between bacteraemia and non-bacteraemic isolation, all clinical isolations was a more sensitive measure for detecting changes in MRSA rates in our Trust over 1998–2006 than bacteraemia alone.
What are the limitations of the proposed surveillance measure, given that, as is likely, practical issues of data collection and computation can be readily addressed by appropriate information technology? Firstly, as we focussed on potentially nosocomially acquired infections, we did not study patients in the first two days of admission, a group we have previously shown to account for about 25% of all hospital bacteraemia in the UK
An additional caveat is that by necessity such a surveillance measure is restricted to clinical samples which happened to be taken, and sampling frequency given particular conditions (such as surgical wounds) may be determined not only by the clinical condition but also by other factors (e.g. local policies). However, this is probably also true of blood cultures, since indications for blood culture are controversial in many clinical settings. We believe these issues are largely irrelevant provided one has a goal of determining success of infection control within an institution, if the sampling indications remain similar over time, which is an assumption behind much passive infectious disease surveillance. Indeed, because of the increased frequency of our outcome measure, we suggest our proposed measure has many advantages over the inherently variable and infrequent bacteraemia based outcome currently used
Information provision to relevant individuals forms part of universally recognised definitions of effective surveillance