Point-of-care testing by healthcare workers for detection of meticillin-resistant Staphylococcus aureus, Clostridioides difficile, and norovirus.

BACKGROUND: The feasibility of introducing three separate Cepheid GeneXpert® assays was assessed: Xpert SA Nasal Complete, Xpert C. difficile, and Xpert Norovirus for point-of-care testing (POCT) on a ward in a district general hospital. AIM: To establish a seven-day/24 h POCT service for meticillin-resistant Staphylococcus aureus (MRSA), Clostridioides difficile, and norovirus operated solely by healthcare workers (HCWs). METHODS: The Cepheid GeneXpert assays performance characteristics were assessed by comparing the assays to traditional central laboratory methods in terms of clinical turnaround times, hands-on time, number of process steps, time to result and diagnostic accuracy. HCW feedback was collected to consider the potential added value of applying this technology to improve patient flow and clinical care. FINDINGS: In total 1170 tests were carried out over the 16-month study period. The assays significantly reduced hands-on time, process steps, and time to result for identification of all three micro-organisms. Overall agreement with central laboratory testing was >98% for all three assays. Staff members fed back that POCT had a positive impact in terms of clinical utility. CONCLUSION: Xpert SA Nasal Complete for MRSA detection, Xpert C. difficile, and Xpert Norovirus can be used as POCT solely by HCWs in a ward setting. Each assay was used throughout a seven-day/24 h period with potential positive impact on bed management and patient care.

A retrospective cohort study into acquisition of MRSA and associated risk factors after implementation of universal screening in Scottish hospitals.

OBJECTIVE: To estimate the proportion of patients who acquire methicillin-resistant Staphylococcus aureus (MRSA) while in hospital and to identify risk factors associated with acquisition of MRSA. DESIGN: Retrospective cohort study. PATIENTS: Adult patients discharged from 36 general specialty wards of 2 Scottish hospitals that had implemented universal screening for MRSA on admission. METHODS: Patients were screened for MRSA on discharge from hospital by using multisite body swabs that were tested by culture. Discharge screening results were linked to admission screening results. Genotyping was undertaken to identify newly acquired MRSA in MRSA-positive patients on admission. RESULTS: Of the 5,155 patients screened for MRSA on discharge, 2.9% (95% confidence interval [CI], 2.43-3.34) were found to be positive. In the subcohort screened on both admission and discharge (n = 2,724), 1.3% of all patients acquired MRSA while in hospital (incidence rate, 2.1/1,000 hospital bed-days in this cohort [95% CI, 1.5-2.9]), while 1.3% remained MRSA positive throughout hospital stay. Three risk factors for acquisition of MRSA were identified: age above 64 years, self-reported renal failure, and self-reported presence of open wounds. On a population level, the prevalence of MRSA colonization did not differ between admission and discharge. CONCLUSIONS: Cross-transmission of MRSA takes place in Scottish hospitals that have implemented universal screening for MRSA. This study reinforces the importance of infection prevention and control measures to prevent MRSA cross-transmission in hospitals; universal screening for MRSA on admission will in itself not be sufficient to reduce the number of MRSA colonizations and subsequent MRSA infections.

Report of a hospital neonatal unit outbreak of community-associated methicillin-resistant Staphylococcus aureus.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) with the type IV staphylococcal chromosomal cassette mec (SCCmec) is rarely reported as being acquired in hospital. We report a hospital outbreak, in Grampian, Scotland, of eight cases of skin and soft-tissue infections due to such a strain. All patients had been in the labour, delivery and maternity units of a small community hospital during a 7-month period. Typing by pulsed-field gel electrophoresis showed the isolates to be a single strain closely related to the USA800 lineage (paediatric clone) and additional typing confirmed it as ST5-MRSA-IV. Genes for exfoliative toxin A (ETA) and enterotoxin D were detected by PCR in all the isolates although none carried the Panton-Valentine leukocidin gene. Region-wide surveillance of over 6000 MRSA isolates collected from 1998 to 2004 showed that 95 (1.6%) were closely related to the outbreak strain although only 60 carried the ETA gene. The strain has not been seen elsewhere in Scotland.

Temporal relationship between prevalence of meticillin-resistant Staphylococcus aureus (MRSA) in one hospital and prevalence of MRSA in the surrounding community: a time-series analysis.

We studied the relationship between meticillin-resistant Staphylococcus aureus (MRSA) prevalence in the Aberdeen Royal Infirmary and in the surrounding community (Grampian region: 500 000 inhabitants). We calculated the monthly %MRSA for both hospital and community from January 1996 to February 2002. A dynamic regression model was adjusted to measure any relationship between both series. The monthly %MRSA in the community was strongly related to the monthly %MRSA observed one month before in the hospital (R(2)=90.8%). We found no relationship with antimicrobial community use, although we have previously reported a strong correlation between prior use of antibiotics and incidence of MRSA in the hospital. By using time-series analysis techniques, we demonstrated that variations in MRSA prevalence in the hospital are quickly followed by similar variations in MRSA prevalence in the surrounding community. These results suggest that the reason for the increase in MRSA prevalence in the community was a hospital MRSA outbreak. Screening at patient discharge should be evaluated as a new measure to control spread of MRSA in the community.

Impact of infection control interventions and antibiotic use on hospital MRSA: a multivariate interrupted time-series analysis.

Hospitals in the northeast of Scotland have experienced methicillin-resistant Staphylococcus aureus (MRSA) outbreaks since 1997. Several infection control measures were introduced sequentially to control MRSA, and antibiotic use has been monitored. From January 1997 to December 2004, data on the monthly percentage of non-duplicate MRSA infections (%MRSA) were collated from an intervention hospital (IH) and a control hospital (CH). Both hospitals introduced the use of alcohol hand gel in November 2002. Furthermore, the IH introduced an environmental MRSA swabbing programme in March 2001, chlorine disinfection of the environment in September 2001, discharge screening in December 2001, admission screening in November 2003 and environmental audits in March 2004. Multivariate dynamic regression analysis was used to evaluate the longitudinal effects of these interventions as measured by new clinical cases of MRSA. At the IH, the %MRSA increased between January 1998 and January 2001 and then decreased. At the CH, the %MRSA increased from January 1997 to December 2004. Introduction of alcohol hand gel was associated with an absolute decrease in %MRSA of 21% and 30%, respectively, for the IH and CH. At the IH, introduction of chlorine disinfection and environmental swabbing were, respectively, associated with a decrease in %MRSA of 27% immediately and 32% 3 months later. Discharge screening and environmental audit did not significantly affect %MRSA, whereas admission screening was associated with a 22% decrease in %MRSA 4 months later. Increasing macrolide use was associated with increasing %MRSA in both hospitals, and increasing quinolone use was associated with increasing %MRSA in the CH. Implementation of stepwise infection control measures was associated with a decrease in %MRSA in the IH. Introduction of an alcohol gel for hand hygiene was associated with a decrease in %MRSA in both hospitals. Antibiotic use also affects %MRSA, in particular that of macrolides and quinolones.

Antimicrobial drug use and infection control practices associated with the prevalence of methicillin-resistant Staphylococcus aureus in European hospitals.

Major regional variations in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) are observed across Europe. This study investigated hospital MRSA prevalence in relation to patterns of antimicrobial use and infection control policies in an observational, cross-sectional study that used retrospective data from 2001 and linear regression to model relationships. MRSA prevalence (median 20.8%, n = 173 hospitals) and antimicrobial consumption (median 55.2 defined daily doses/100 bed-days, n = 140 hospitals) both varied significantly according to geographical region (p <0.001). MRSA prevalence and antimicrobial consumption data were provided by 128 hospitals, and showed a strong statistical relationship between macrolide use and MRSA prevalence. Use of (i) third-generation cephalosporins, (ii) all antimicrobial agents, and (iii) all antimicrobial agents except glycopeptides was also associated with MRSA prevalence. Up to 146 hospitals provided data on MRSA prevalence and key infection control parameters. Adjusted linear regression modelling provided strong evidence that infection control policy recommendations associated with lower MRSA prevalence rates were (i) use of alcohol-based solutions for hand hygiene (mean difference 10.3%, 99% CI 1.2-10.3), and (ii) placement of MRSA patients in single rooms (mean difference 11.2%, 99% CI 1.4-20.9). Hospitals with problems in implementing isolation policies had higher resistance levels (mean difference 12%, 99% CI 3.8-20.1). Additional recommendations showed less evidence of association with a low MRSA prevalence. Overall, this study highlighted significant associations between MRSA prevalence, antimicrobial use and various key infection control parameters, all of which showed significant individual variations according to geographical region.

Antimicrobial susceptibility testing in European hospitals: report from the ARPAC study.

This observational study describes the antimicrobial susceptibility testing (AST) methods and interpretive criteria used in European hospitals during 2001, focusing specifically on detection of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Of 263 hospitals that took part in the ARPAC study, 192 submitted data on AST. Of these, 89% (n = 170) routinely used a disk-diffusion AST method, 43% (n = 82) used a semi-automated method, and 70% (n = 135) routinely determined MICs. Hospitals in southern Europe were less likely to use disk-diffusion, but were more likely to use a semi-automated method (p <0.001). In total, 173 (90%) interpreted AST results using CLSI breakpoints; 30% of these detected MRSA using unmodified CLSI disk-diffusion methods, while 35% used the unmodified CLSI agar-screening method for MRSA; 41% and 30% adhered to unmodified CLSI methodology for disk-diffusion and agar-screening, respectively, to detect VRE. Some of the modifications made may have greatly reduced the ability of the tests to detect MRSA/VRE. For example, 20% of respondents used excessively high incubation temperatures and 13% used inadequate incubation times to detect MRSA by disk-diffusion, and 28% used Mueller-Hinton agar instead of brain-heart infusion agar in VRE screening plates. The majority of respondents stated that they followed CLSI guidelines, but a high proportion had modified the CLSI methods for detecting MRSA and VRE, which may compromise clinical management and antimicrobial resistance surveillance.

Status of infection control policies and organisation in European hospitals, 2001: the ARPAC study.

Patient safety in hospital care depends on effective infection control (IC) programmes. The Antimicrobial Resistance Prevention and Control (ARPAC) study assessed the organisation, components and human resources of IC programmes in European hospitals. A questionnaire survey of policies and procedures implemented in 2001 for the surveillance and control of nosocomial infection and antibiotic resistance was completed by 169 acute-care hospitals from 32 European countries, categorised by five geographical regions. A formal IC programme existed in 72% of hospitals, and a multidisciplinary IC committee was operational in 90%. Trained IC nurses (ICNs) were present in 80% of hospitals (ranging from 54% in south-east and central-eastern Europe, to 100% in northern Europe), whereas 74% had one or more trained IC doctors (ICDs) (ranging from 46% in south-east Europe to 84% in western Europe). Median staffing levels were 2.33 ICNs/1,000 beds and 0.94 ICDs/1,000 beds. The intensity of IC programmes scored higher in centres from northern and western Europe than from other European regions. Written guidelines promoted hand hygiene for healthcare workers in 89% of hospitals, education in 85%, and audit in 46%. Guidelines recommended use of alcohol-based solutions (70%) and/or medicated/antiseptic soap (43%) for decontamination of non-soiled hands. Use of alcohol-based solutions varied according to region, from 41% in southern Europe to 100% in northern Europe, compared with use of medicated soap from 77% in southern Europe to 11% in northern Europe (p < 0.01). These findings showed that IC programmes in European hospitals suffer from major deficiencies in human resources and policies. Staffing levels for ICNs were below recommended standards in the majority of hospitals. Education programmes were incomplete and often not supported by audit of performance. Hand hygiene procedures were sub-standard in one-third of centres. Strengthening of IC policies in European hospitals should be a public health priority.

Report of the Consensus Conference on Antibiotic Resistance; Prevention and Control (ARPAC).

Antimicrobial resistance is a key public health concern in Europe. It is known that there are significant variations in the prevalence of resistance across Europe, and methods to reduce the problem are also assumed to vary significantly. The 'Antibiotic Resistance; Prevention and Control (ARPAC)' Concerted Action project was funded by the European Commission and conducted by four study groups of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). The project established a network of European hospitals and collated data on antimicrobial resistance prevalence, antimicrobial susceptibility testing methods, typing methods employed, antimicrobial use, antibiotic policies and practices, and infection control policies and practices. The ARPAC Consensus Conference, entitled 'Control of antibiotic resistance in European hospitals-informing future evidence-based practice', was held in Amsterdam in November 2004. The conference was co-hosted by the European Commission, ESCMID and the Dutch Working Party on Antibiotic Policy (SWAB). Key ARPAC findings were presented and discussed in the context of the worldwide situation. The conference delivered a set of high-priority recommendations likely to have a significant impact on antimicrobial resistance. This report summarises these recommendations.

Antibiograms of resistant Gram-negative bacteria from Scottish CF patients.

BACKGROUND: Over a 19-month pilot phase, 93 multiply resistant Gram-negative isolates from Scottish cystic fibrosis patients were sent to a referral laboratory for further investigation. METHODS: In common with the referring diagnostic laboratories, disc diffusion testing was carried out. Antibiotic susceptibility testing was also established by MIC methodology. NCCLS methods were used throughout. Twenty antibiotics were tested. RESULTS: Comparing disc diffusion results against MIC results, there were 167 (14%) major errors. By MIC, Pseudomonas aeruginosa (n = 59), Stenotrophomonas maltophilia (n = 16), Burkholderia cepacia (n = 10) and Alcaligenes xylosoxidans (n = 7) were susceptible to 18%, 11%, 4% and 35% of the antibiotics tested, respectively. Colistin and tobramycin were the most active agents against P. aeruginosa with 60% and 49%, respectively, testing susceptible. Minocycline and gentamicin were most active against S. maltophilia with 58% and 18%, respectively, testing susceptible. B. cepacia were most susceptible to co-trimoxazole (10%) and ciprofloxacin (10%). Five and six of the seven A. xylosoxidans isolates were susceptible to piperacillin and imipenem, respectively. CONCLUSIONS: Improved methods for susceptibility testing of such clinical isolates need to be employed in routine diagnostic laboratories. Levels of resistance in referred isolates were very high and similar to those described in the USA.

Reassessment of cefaclor breakpoints for Haemophilus influenzae.

We previously reported that standard methods overestimate cefaclor minimum inhibitory concentrations (MICs) for Streptococcus pneumoniae due to in vitro chemical instability. This study aimed to ascertain if standard methods accurately measure cefaclor MICs to Haemophilus influenzae. Cefuroxime was used as a comparator. Standard NCCLS broth microdilution and E-Test MICs were determined for eight isolates of H. influenzae. Kill curves determined the "bacteriostatic" MIC, defined as the concentration showing no significant growth or kill over six hours taking into account cefaclor instability. On average, cefaclor and cefuroxime bacteriostatic MICs were 0.2 x MIC and 0.6 x MIC determined by NCCLS methodology respectively. The mean MIC determined by NCCLS methodology was 3.0 mg/L for cefaclor and 0.8 mg/L for cefuroxime. Cefaclor MICs by NCCLS methodology were overestimated due to chemical instability over 18-24 hours. The bacteriostatic MICs by kill curve were not significantly different from those of cefuroxime.

Antibiotic exposure as a risk factor for emergence of resistance: the influence of concentration.

Evolution of antibiotic resistance (AR) is increasingly perceived as a major clinical problem. The use of bactericidal antibiotics may protect against this, to some extent, by eradication of the pathogen, but the borders between cidal and inhibitory activity in the patient are often blurred. In addition, there are clinical reasons why eradication of the pathogen may not always be desirable. Antibiotic dosing schedules are currently driven by the perception that T > MIC and AUIC are the main predictors of outcome for time-dependent and concentration-dependent antibiotics, respectively. In the context of protecting against development of resistance in the pathogen however, peak antibiotic concentration and the concept of mutant prevention concentrations may be more important. The role of post-antibiotic and sub-MIC effects is more conjectural. Considerations of mechanisms of resistance and their relationship to antibiotic dosing schedules will also be highlighted. Lastly, the relevance of all this to the development of resistance in the normal bacterial flora will be discussed.

Molecular epidemiology and antibiotic resistance of Enterobacter spp. from three distinct populations in Grampian, UK.

The distribution of Enterobacter spp. within the population of Aberdeen Royal Infirmary was compared with the outpatient population with regard to molecular epidemiology and antibiotic resistance. Enterobacter spp. from 60 patients and one environmental site were characterised as ITU, non ITU and outpatients' isolates. Thirty-five percent were blood culture isolates. Cefotaxime resistant strains in the hospital were frequent. Cefotaxime (64%) sensitive isolates were inducible for hyperproduction of Bush group 1 beta-lactamase. Isolates were further investigated by PFGE. Isolates (27%) were clonally related and typed in four clusters. Consecutive isolates were studied in selected patients showing minor genomic changes. One environmental isolate from a deep sink at ITU was related to a patient's isolate.

Comparison of screening methods for TEM- and SHV-derived extended-spectrum beta-lactamase detection.

OBJECTIVE: To compare common extended-spectrum beta-lactamase (ESBL) screening methods and beta-lactams for their ability to detect TEM- and SHV-related ESBL enzymes. METHODS: This study compared disk diffusion testing by NCCLS methodology, the Jarlier double disk test, a disk-on-disk test, a modified three-dimensional test and the E test method for their sensitivity and specificity in detecting TEM- and SHV-related ESBL producers. Three negative and 22 positive controls were studied. These were two Klebsiella pneumoniae and 23 Escherichia coli transconjugants. Seventeen beta-lactam antibiotics were tested: cefamandole, cefotetan, cefoxitin, cefuroxime, cefixime, cefoperazone, cefotaxime, cefpodoxime, cefsulodin, ceftazidime, ceftibuten, ceftizoxime, ceftriaxone, moxalactam, cefepime, cefpirome and aztreonam. RESULTS: NCCLS disk diffusion was 14% sensitive with ceftriaxone, 36% with cefotaxime, 64% with aztreonam, 68% with cefpodoxime, and 73% with ceftazidime. Cefoperazone, cefamandole, cefpodoxime and cefpirome showed 91% sensitivity using the Jarlier test. Using the disk-on-disk test, cefsulodin showed 95% sensitivity, and cefoperazone, cefepime and cefamandole showed 91% sensitivity. With the modified three-dimensional test, cefoperazone, cefpodoxime and cefpirome showed 91% sensitivity. CONCLUSIONS: For practical reasons, we would recommend use of either the Jarlier test or the commercial cephalosporin disks containing clavulanic acid to screen for ESBL producers. Cefoperazone, cefamandole, cefpodoxime and cefpirome showed good sensitivity across the methods tested.

Antibiotic exposure as a risk factor for emergence of resistance: the influence of concentration.

Evolution of antibiotic resistance (AR) is increasingly perceived as a major clinical problem. The use of bactericidal antibiotics may protect against this, to some extent, by eradication of the pathogen, but the borders between cidal and inhibitory activity in the patient are often blurred. In addition, there are clinical reasons why eradication of the pathogen may not always be desirable. Antibiotic dosing schedules are currently driven by the perception that T >MIC and AUIC are the main predictors of outcome for time-dependent and concentration-dependent antibiotics, respectively. In the context of protecting against development of resistance in the pathogen however, peak antibiotic concentration and the concept of mutant prevention concentrations may be more important. The role of post-antibiotic and sub-MIC effects is more conjectural. Considerations of mechanisms of resistance and their relationship to antibiotic dosing schedules will also be highlighted. Lastly, the relevance of all this to the development of resistance in the normal bacterial flora will be discussed.

Chorionicity determination in twin pregnancies: how accurate are we?

OBJECTIVES: To determine the accuracy of antenatal prediction of chorionicity in twin pregnancies in our institution. METHODS: Antenatal chorionicity was determined using the number of placental masses, the presence or absence of a twin peak sign and the fetal sex. The gestational age at assessment was documented. Postnatal diagnosis of chorionicity was determined by neonatal sex and placental pathology. RESULTS: Chorionicity was correctly determined in 95% of cases (n = 131); 91% of the monochorionic and 96% of the dichorionic pregnancies were correctly determined. If chorionicity was assessed prior to 14 weeks' gestation (n = 96) the correct diagnosis was made in all except one case. CONCLUSIONS: Ultrasound assessment of chorionicity has a high sensitivity and specificity. This is further improved if the assessment is performed prior to 14 weeks' gestation.

Protected environments allow parallel evolution of a bacterial pathogen in a patient subjected to long-term antibiotic therapy.

Long-term antibiotic treatment offers a rare opportunity to study the evolution of bacteria within the same individual. The appearance of new variants has been suggested to take place via the selection of enhanced resistance in compartments of the body in which the antibiotic concentration is low. Laboratory models of protected compartments have elegantly demonstrated their potential in selecting novel variants. However, comparable data from patients have been rare. In this study, extended antibiotic therapy in a single patient suffering from multiple infected liver cysts has provided the opportunity to observe and analyse the molecular evolution of antibiotic resistance. Each isolate has the same basic ompC gene sequence that is distinct from other Escherichia coli isolates, which suggests that they derive from the same founder population. However, the isolates differ in their auxotrophic markers, in the pI values of their dominant beta-lactamase activities and in the mutations in the promoter region of the ampC gene leading to increased expression of the AmpC enzyme. The data provide strong evidence for a single focal infection expanding via parallel pathways of evolution to give a range of antibiotic-resistant isolates. These data suggest that the infected cysts provide numerous protected environments that are the foci for the separate development of distinct variants.