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Orthopaedic antimicrobial prophylaxis in the United Kingdom
Abstract
Using the Freedom of Information Act, a five-point questionnaire was sent to all NHS Trusts in the United Kingdom: Eighty
two per cent of NHS Trusts in the UK who had an orthopaedic department replied. The top three antimicrobial prophylaxis regimes
in orthopaedic surgery were cefuroxime alone (trauma 48%, elective 56%), flucloxacillin plus gentamicin (trauma 16%, elective
19%) and co-amoxiclav alone (trauma 10%, elective 5.6%). Forty nine per cent of Trusts involved changed antimicrobial prophylaxis
regimes between August 2005 and July 2008, to restrict the use of cefuroxime. There was a 74% difference in C. difficile rates in Trusts who use cefuroxime when compared to any other antimicrobial regime. In Trusts that changed away from cefuroxime,
there was a 33% reduction in C. difficile rates. Clostridium difficile rates were six times higher in trauma than elective surgery across the UK. Few Trusts (trauma 7.7%, elective 7.6%) used antimicrobial
prophylaxis regimes that have a low-risk association with C. difficile infection.
KeywordsAntimicrobial prophylaxis–
Clostridium difficile
–Cephalosporins
... 36,37 C difficile is far less of a problem among elective orthopaedic patients than trauma orthopaedic patients, with reported incidences of 0.1-0.17%. 35,38 Jenkins et al concluded that, given the low incidence of C difficile in arthroplasty patients, cephalosporins were a safe option as antimicrobial prophylaxis in elective surgery. 38 C difficile continues to be an important cause of morbidity and mortality in orthopaedic trauma patients and measures must be put in place to reduce risk factors. ...
... 36 We have demonstrated previously how trusts changing away from cephalosporins reduced their C difficile infection rates in orthopaedic surgery significantly. 35 Al-Obaydi et al mirrored this message after a change away from cefuroxime in a single unit reduced C difficile infections. 39 Teicoplanin Teicoplanin is a glycopeptide antimicrobial agent that offers high soft tissue and bone penetration. ...
Antimicrobial prophylaxis remains the most powerful tool used to reduce infection rates in orthopaedics but the choice of antibiotic is complex. The aim of this study was to examine trends in antimicrobial prophylaxis in orthopaedic surgery involving the insertion of metalwork between 2005 and 2011.
Two questionnaires (one in 2008 and one in 2011) were sent to all National Health Service trusts in the UK using the Freedom of Information Act.
In total, 87% of trusts that perform orthopaedic surgery responded. The use of cefuroxime more than halved between 2005 and 2011 from 80% to 36% and 78% to 26% in elective surgery and trauma surgery respectively. Combination therapy with flucloxacillin and gentamicin rose from 1% to 32% in elective and 1% to 34% in trauma surgery. Other increasingly popular regimes include teicoplanin and gentamicin (1% to 10% in elective, 1% to 6% in trauma) and co-amoxiclav (3% to 8% in elective, 4% to 14% in trauma). The majority of changes occurred between 2008 and 2010. Over half (56%) of the trusts stated that Clostridium difficile was the main reason for changing regimes.
In 2008 a systematic review involving 11,343 participants failed to show a difference in surgical site infections when comparing different antimicrobial prophylaxis regimes in orthopaedic surgery. Concerns over C difficile and methicillin resistant Staphylococcus aureus have influenced antimicrobial regimes in both trauma and elective surgery. Teicoplanin would be an appropriate choice for antimicrobial prophylaxis in both trauma and elective units but this is not reflected in its current level of popularity.
... 31 The importance of government being able to debate in confidence, to allow civil servants to give frank analysis and the negative reporting employed by the mass media were other key issues that the former Prime Minister raises in his memoirs. 17 In the era of open access research and preregistration of trial information and protocols on publically accessible databases, having raw data available openly is a key aspect of academic freedom. 32 In an increasingly connected world, data being easily available allows timely dissemination of important advances and findings. ...
To assess the use and utility of the Freedom of Information Act (2000) in healthcare research since 2005 and to determine if any particular feature of studies found led to greater data acquisition.
PRISMA compliant systematic review.
An extensive literature search was performed of EMBASE, MEDLINE, CINAHL, psychINFO, BNI, AMED, HMIC and Health business elite databases from January 2005 to January 2013 using terms 'Freedom of information', 'Freedom of information act' and 'Freedom of information act 2000'. Papers were considered for publication if they described utilising the UK Freedom of information act to gather data for healthcare research. 16 articles met these criteria.
Primary outcome was the number and characteristics of studies utilising the Freedom of Information Act to collect the data for healthcare research. Secondary outcome measures were any features that improved data acquisition rates (including to whom the request was made, the number of questions asked per request, etc.) RESULTS: 16 articles described utilising the Freedom of Information Act for healthcare research, and these investigated a broad range of topics. The median number of requests made was 86 (range 1-172), the total number of requests was 1732. A total of 15 817 pieces of data were retrieved by all studies. The amount of data collected was defined as the number of questions asked multiplied by the number of full responses. A median of five questions were asked per study (range 5-6.5) and the overall response rate was 86%. The National Health Service litigation authority responded to 100% of requests, while Primary Care Trusts had the lowest response rate of 81% for healthcare bodies. A positive correlation between number of requests made and data obtained (0.508, p<0.05) and number of requests made and increased response rate (0.737, p<0.01), both reached the statistical significance.
Researchers should make greater use of the Act to access the information they need that is not otherwise disclosed. We discuss the issues with the research utilising the Act and how future research of this type could be optimised.
Toxin-producing Clostridium difficile is the commonest bacterial cause of nosocomial diarrhoea and is a well recognized cause of hospital outbreaks in elderly care units. High C. difficile disease rates have been associated with the use of broad-spectrum antibiotics, especially cephalosporins. An outbreak of C. difficile infection in the elderly care unit at Gloucestershire Royal NHS Trust continued despite increased ward cleaning and strict implementation of infection control measures. A restrictive antibiotic policy that would maintain colonization resistance in the gastrointestinal tract was introduced throughout this unit. Patients admitted with suspected infection were prescribed intravenous (i.v.) benzylpenicillin 1.2-1.8 g every 6 h to cover streptococcal infections and i.v. trimethoprim 200 mg twice daily to cover urinary tract pathogens and Haemophilus influenzae. If the patient had septic shock a single iv dose of gentamicin was given (120- 180 mg) to cover more resistant gram-negative bacilli. The following were monitored before and after the policy change. The number of cases of C. difficile toxin-positive diarrhoea; cefuroxime and total antibiotic use on the elderly care wards; patient mortality rates; and length of hospital stay: two hundred and fifty-two and 234 patients respectively with a discharge diagnosis of infection were admitted before and after the antibiotic policy change. Mortality rates and length of hospital stay were unchanged. Cefuroxime prescribing and total antibiotic prescribing costs fell by 5150 pounds sterling and 8622 pounds sterling respectively in the 7 month period after the change. Thirty-seven cases of C. difficile diarrhoea occurred in the period before and 16 in the period after the policy change. The incidence of C. difficile diarrhoea and of cefuroxime use has remained low since then. The use of narrow-spectrum antibiotics for hospital treatment of community-acquired infections in the elderly should be encouraged. Outbreaks of C. difficile diarrhoea should be managed with the combined approach of infection control and strict antibiotic policies.
Increasing rates of Clostridium difficile infection (CDI) with an unusual, severe course have been reported in several countries; this rise has partly been ascribed to the emergence of a virulent strain, C. difficile PCR ribotype 027 (CD027). An intriguing question is whether this could be related to increasing consumption of broadspectrum antibiotics. From 1997 to 2007, the number of hospital discharges in Denmark with the diagnosis enterocolitis caused by C. difficile increased from eight to 23 per 100,000 hospital discharges. This increase was proportional to a concomitant rise in the consumption of fluoroquinolones and cephalosporins. The first outbreak of CD027 in Denmark occurred from October 2006 to August 2007 and included 13 patients, most of them elderly, admitted to three hospitals in the same region. Most of the patients had overlapping periods of admission. All patients had been treated with broadspectrum antibiotics, in particular cephalosporins and fluoroquinolones, prior to positive culture of CD027. 30 days after confirmation of diagnosis, three of the 13 patients had died. Taken together, the data support the hypothesis that the increasing use of certain broadspectrum antibiotics may be related to a possible increase of C. difficile infection, and show that the specific contribution by CD027 in its emergence needs to be determined.
A total of 108 volunteers undergoing an elective surgical procedure were randomly given a single 2-g intravenous prophylactic
dose of either a cephalosporin or mezlocillin. Stool samples were cultured for Clostridium difficile the day before the operation
and later on postoperative days 4, 7, and 14. C. difficile was detected in 23.0% of patients who received a cephalosporin
(cefoxitin, 8.3%; cefazolin, 14.3%; cefotetan, 20.0%; ceftriaxone, 25.0%; cefoperazone, 43.7%), in 3.3% of patients given
mezlocillin, and in none of 15 control volunteers given no antimicrobial agent. No patient experienced diarrhea.
Orthopaedic joint replacement is generally considered 'clean' surgery characterized by a low incidence of infection. In recent years the use of a clean theatre environment, high local concentrations of antibiotic in the cement and systemic antibiotic prophylaxis have been recognized as important measures to reduce infection rates significantly, and this has been supported by clinical trials. Staphylococcus aureus and Staphylococcus epidermidis cause at least half of all orthopaedic surgical infections. Gram-negative bacilli are involved to a much lesser extent (10-30%). First- and second-generation cephalosporins are currently considered by most authors as standard prophylaxis in elective orthopaedic surgery. In the light of the increasing incidence of methicillin resistance in coagulase-positive and -negative staphylococci, it is becoming more important for antibiotics to act efficiently against such organisms if they are to be of value in prophylaxis in orthopaedic surgery. A combined, single-dose of vancomycin/gentamicin has been used successfully in an open, controlled study in patients undergoing total joint arthroplasty but, given the disadvantages associated with the use of vancomycin, teicoplanin may be an alternative choice in such procedures. This review analyses four comparative trials of the efficacy and safety of teicoplanin, two with cefamandole, one with cefuroxime and one with cephazolin, as prophylaxis in orthopaedic total joint replacement surgery.
The cephalosporin antibiotics have become a major part of the antibiotic formulary for hospitals in affluent countries. They are prescribed for a wide variety of infections every day. Their undoubted popularity relies upon lesser allergenic and toxicity risks as well as a broad spectrum of activity. It is the latter feature, however, that encourages the selection of microorganisms that are resistant to these agents. There are long-term implications for the treatment and control of this heterogeneous group of superinfections. When clinicians evaluate a septic patient, it is understandable that they choose empirical therapy with a cephalosporin whilst awaiting microbiology and other tests, since bacterial identification and antimicrobial testing still usually require 24-48 h. The broad-spectrum capability of these drugs, however, encourages rapid overgrowth of some microorganisms that are neither eliminated nor inhibited by therapy. These organisms not only have pathogenic potential, they may also be multiply resistant to antibiotics. This review discusses the evidence that cephalosporin usage is the most important factor in the selection and propagation of microorganisms such as Clostridium difficile, methicillin-resistant Staphylococcus aureus, penicillin-resistant pneumococci, multiply resistant coliforms and vancomycin-resistant enterococci, the continuing increase of which threatens the future of antimicrobial therapy.
Antibiotic-associated Clostridium difficile diarrhoea may complicate recovery from surgery for proximal femoral fracture. We undertook a four-year case-control study to evaluate a change in antibiotic prophylaxis in our department. During the period January 2003 to January 2005, patients received three doses of prophylactic cefuroxime (1.5g). We then introduced a new regimen, comprising of one single dose of cefuroxime (1.5g) with gentamicin (240mg) at induction. Prior to the change in prophylaxis, 912 patients underwent surgery for neck of femur fracture, and from March 2005 to March 2007, 899 patients had surgery under the new regimen. Thirty-eight patients developed C. difficile infection (4.2%) in the initial group, compared with 14 patients (1.6%) in the group with the new regimen (P=0.009). The incidence of C. difficile infection increased throughout the rest of the hospital over the same time period. Patients with C. difficile infection had a statistically significant increase in antibiotic exposure, inpatient stay, morbidity and inpatient mortality. The main challenges regarding prophylactic antibiotic selection are infection due to meticillin-resistant Staphylococcus aureus (MRSA) and C. difficile-associated diarrhoea. We advocate the use of the new regimen as an alternative to multiple-dose cephalosporin antibiotics for the prevention of C. difficile infection in this group of high-risk patients.
The first Dutch outbreak due to
Clostridium difficile
ribotype 027 was observed in mid-2005;
by the end of that year, eight hospitals were affected. To study the relationship between hospital-
wide antibiotic use and the incidence of 027-linked
C. difficile
-associated disease (CDAD) three
study groups were made: group A, all eight hospitals with an 027-associated epidemic; group
B, five of a total of six hospitals with occasional 027 cases, without an increase in CDAD; and
group C, ten randomly selected hospitals with no reported 027 epidemics or isolated 027 cases.
Quarterly data on CDAD incidences, hygiene measures and the use of fluoroquinolones, second-
and third-generation cephalosporins, extended-spectrum penicillins, penicillins with beta-
lactamase inhibitors, carbapenems, lincomycins and macrolides were collected for 2004 and
2005, and divided into pre-epidemic and epidemic periods. Using a multilevel Poisson regression
analysis, CDAD incidence was linked to antibiotic use in the previous quarter and to certain
hygiene measures. In the pre-epidemic period, the total use of the studied antibiotics was
comparable between affected and unaffected hospitals. Higher use of second-generation
cephalosporins, macrolides and all of the studied antibiotics were independently associated with
a small increase in CDAD incidence
[
relative risk (95% confidence interval): 1.14 per increase of
100 defined daily doses per 10000 bed days (1.06–1.23), 1.10 (1.01–1.19) and 1.02 (1.01–
1.03), respectively
]
. However the effect was too small to predict which hospitals might be more
prone to 027-associated outbreaks.
A series of infection control measures were introduced at the University Hospitals of Leicester NHS Trust in 2006-2007 to reduce the incidence of Clostridium difficile infection.
The aim of this study was to assess the impact of these measures on the incidence of C. difficile and to record the associated mortality in hip fracture patients.
A case matched comparison of mortality was conducted between C. difficile positive patients and C. difficile negative patients admitted with a hip fracture between 1st January 2003 and 30th September 2007. An interrupted time series analysis was performed to assess the effect of various infection control policies on the incidence of C. difficile infection.
The interrupted time series analysis showed that the only effective measure was changing antimicrobial prophylaxis to Co-amoxiclav in May 2007. This reduced the incidence of C. difficile from 7.1 to 1.5% (p<0.001). Six-month mortality in C. difficile positive patients was 71% 1 year before introduction of a diarrhoea treatment policy and 65% 1 year after (p=0.5) indicating treatment was ineffective. A matched cohort comparison over a 57-month period from January 2003 to September 2007 showed that the 6-month mortality was 67% in 170 C. difficile positive patients, 27% in 3247 C. difficile negative patients and 29% in the 170 C. difficile negative matched patients.
This 38% excess mortality indicated that C. difficile increased mortality and did not simply colonise the sickest patients. Changing prophylaxis to Co-amoxiclav was the most effective measure. This reduced the incidence of C. difficile by 80% and thus reduced mortality by prevention rather than cure.
The current measures employed by consultant orthopaedic surgeons in Scotland to prevent infection were established by postal questionnaire. Our findings were compared with those of a similar study carried out 5 years previously. An increasing number of surgeons use routine systemic antibiotic prophylaxis for total hip arthroplasty (99% versus 91% 5 years ago), in treating compound fractures (89% versus 75% 5 years ago) and for internal fixation of closed fractures with metal implants (49% versus 12% 5 years ago). Cephalosporins are increasingly used as the antibiotic of choice. By starting antibiotics earlier than the day of surgery or continuing for more than 24 h after surgery, just over half the surgeons questioned administer antibiotics for longer than would seem to be necessary for elective surgery.
To better define the role of multiple risk factors for cytotoxic Clostridium difficile-associated diarrhea.
Case-control study.
A Veterans Affairs Medical Center.
Thirty-three case patients with C difficile-associated diarrhea. Two control groups were used: one group consisted of 32 patients from the same ward as the case patients, and one group consisted of 34 patients with nosocomial diarrhea and negative C difficile toxin assays.
None.
Multivariate analyses revealed that exposure to second- or third-generation cephalosporins was the most important independent risk factor, even after controlling for other antimicrobial use (odds ratio [OR] = 8.3, 95% confidence interval [CI95] = 1.4 to 48.9 compared to ward controls; OR = 9.6, CI95 = 2.1 to 44.1 compared with diarrhea controls). Persons exposed to two or more antimicrobials simultaneously were at substantially elevated risk (OR = 18.7, CI95 = 4.1 to 85.8 compared with ward controls; OR = 21.5, CI95 = 3.2 to 141.9 compared with diarrhea controls).
Physicians should consider carefully the appropriateness of second- and third-generation cephalosporin use and combination antimicrobial therapy, especially during nosocomial C difficile-associated diarrhea outbreaks (Infect Control Hosp Epidemiol 1994;15:88-94).
High Clostridium difficile disease rates were originally associated with clindamycin use, but this association has declined in recent years following the decline in the clinical use of clindamycin, and disease is now particularly associated with the use of broad-spectrum antibiotics, especially the cephalosporins. There are now sufficient reports in the literature to merit the discontinuation of the widespread use of cephalosporins, especially in the elderly, by the substitution, wherever possible, with antibiotics not associated with the promotion of C. difficile-associated disease. Such agents include benzylpenicillin, gentamicin, trimethoprim, ciprofloxacin and the ureido-penicillins. Widespread education about the proper use of antibiotics in clinical practice remains essential.
Clostridium difficile causes 300 000 to 3 000 000 cases of diarrhea and colitis in the United States every year. Antibiotics most frequently associated with the infection are clindamycin, ampicillin, amoxicillin, and cephalosporins, but all antibiotics may predispose patients to C difficile infection. The clinical presentation varies from asymptomatic colonization to mild diarrhea to severe debilitating disease, with high fever, severe abdominal pain, paralytic ileus, colonic dilation (or megacolon), or even perforation. The most sensitive and specific test available for diagnosis of C difficile infection is a tissue culture assay for the cytotoxicity of toxin B. However, this test takes 1 to 3 days to complete and requires tissue culture facilities. Detection of C difficile toxin by means of enzyme-linked immunoassay is more rapid and inexpensive. A minority of patients may require more than 1 stool assay to detect toxin. Oral metronidazole or oral vancomycin hydrochloride for 10 to 14 days are equally effective at resolving clinical symptoms; oral metronidazole is preferred in most cases because of lowered cost and less selective pressure for vancomycin-resistant organisms. Approximately 15% of patients experience relapse after initial therapy and require retreatment, sometimes with an extended, tapering regimen. Immunity appears to be incomplete and predominantly mediated by serum IgG to toxin A. Measures for preventing the spread of the pathogen, appropriate diagnostic testing, and treatment may avert morbidity and mortality due to C difficile-associated diarrhea.
Broad-spectrum antibiotics, particularly intravenous cephalosporins, are associated with Clostridium difficile diarrhoea. Diarrhoea due to C. difficile is a growing problem in hospitals, especially among elderly patients.
To establish whether changing an antibiotic policy with the aim of reducing the use of injectable cephalosporins leads to a reduction in the incidence of C. difficile diarrhoea in elderly patients.
Retrospective analysis.
A group of patients who were subject to the new antibiotic policy from the period following July 2000, were compared with patients who were admitted prior to July 2000 and were not subject to the new policy. Infections, antibiotic prescriptions and mortality rates were determined from case notes, and C. difficle diarrhoea rates from microbiological data.
Intravenous cephalosporin use fell from 210 to 28 defined daily doses (p < 0.001) following the change in antibiotic policy, with a corresponding increase in piperacillin-tazobactam (p < 0.001) and moxifloxacin (p < 0.001) use. The new policy led to a significant reduction in C. difficile diarrhoea cases. The relative risk of developing C. difficile infection with the old policy compared to the new policy was 3.24 (95%CI 1.07-9.84, p = 0.03).
The antibiotic policy was successfully introduced into an elderly care service. It reduced both intravenous cephalosporin use and C. difficile diarrhoea.
Patients undergoing orthopedic surgery are at increased risk for infection, and antimicrobial use continues to be required. Antimicrobial selection, however, is an important consideration given the increasing incidence and severity of C. difficile infection described in the literature. When choosing antimicrobials for prophylaxis and treatment, evaluate patients for risk factors that may predispose them to C. difficile infection. Patients receiving multiple antibiotics or broad-spectrum antibiotics, women, patients with concurrent proton pump inhibitor use, and those with renal failure are at increased risk. Choice of antibiotics should be evaluated for their potential or likelihood to cause C. difficile infection. When a number of these risk factors are present, avoiding the use of high-risk antibiotics may be warranted.
A meta-analysis of randomised controlled trials evaluated the effectiveness and safety of teicoplanin compared to first- or second-generation cephalosporins for perioperative anti-infective prophylaxis in orthopaedic and vascular surgery involving prosthetic material. No differences were found between teicoplanin and cephalosporins with respect to the development of infection at the site of surgery or in remote areas of the body. In addition, there were no significant differences in reported adverse effects or mortality. These findings indicate that both regimens are equally effective in preventing post-operative infections in orthopaedic and vascular surgery involving prosthetic materials.
The first Dutch outbreak due to Clostridium difficile ribotype 027 was observed in mid-2005; by the end of that year, eight hospitals were affected. To study the relationship between hospital-wide antibiotic use and the incidence of 027-linked C. difficile-associated disease (CDAD) three study groups were made: group A, all eight hospitals with an 027-associated epidemic; group B, five of a total of six hospitals with occasional 027 cases, without an increase in CDAD; and group C, ten randomly selected hospitals with no reported 027 epidemics or isolated 027 cases. Quarterly data on CDAD incidences, hygiene measures and the use of fluoroquinolones, second- and third-generation cephalosporins, extended-spectrum penicillins, penicillins with beta-lactamase inhibitors, carbapenems, lincomycins and macrolides were collected for 2004 and 2005, and divided into pre-epidemic and epidemic periods. Using a multilevel Poisson regression analysis, CDAD incidence was linked to antibiotic use in the previous quarter and to certain hygiene measures. In the pre-epidemic period, the total use of the studied antibiotics was comparable between affected and unaffected hospitals. Higher use of second-generation cephalosporins, macrolides and all of the studied antibiotics were independently associated with a small increase in CDAD incidence [relative risk (95% confidence interval): 1.14 per increase of 100 defined daily doses per 10,000 bed days (1.06-1.23), 1.10 (1.01-1.19) and 1.02 (1.01-1.03), respectively]. However the effect was too small to predict which hospitals might be more prone to 027-associated outbreaks.
Epidemic Clostridium difficile-associated diarrhea: role of second- and third-generation cephalosporins
- D E Nelson
- S B Auerbach
- A L Baltch
- E Desjardin
- C Beck-Sague
- C Rheal
- DE Nelson