Healthcare-worker-associated outbreak of Panton-Valentine-leukocidin-producing meticillin-sensitive Staphylococcus aureus in a large neonatal unit in London: successful targeted suppression therapy following failure of mass suppression therapy.

BACKGROUND: Staphylococcus aureus is a leading cause of healthcare-associated infection, and outbreaks have been associated with neonatal units and colonization of healthcare workers. AIM: To describe an outbreak of Panton-Valentine-leukocidin-producing meticillin-sensitive Staphylococcus aureus (PVL-MSSA) in a neonatal intensive care unit. METHODS: Multi-disciplinary outbreak control investigation. RESULTS: Over a period of 16 months, seven neonates were identified as positive for PVL-MSSA. Isolates were identified in blood cultures (two patients), nasopharyngeal aspirate (one patient) and rectal screening swabs (four patients). Epidemiological and whole-genome sequencing data suggested a long-term carrier as the most likely source. Despite two rounds of mass suppression therapy of staff, using chlorhexidine initially followed by octenidine-based regimens, positive patients continued to be identified. Staff screening subsequently identified one healthcare worker colonized with the outbreak strain of PVL-MSSA who underwent enhanced screening and further suppression therapy. No further cases have been identified to date. Compliance with mass suppression therapy was >95% and a post-administration staff satisfaction survey showed that the majority of staff agreed with the steps taken, with low rates of adverse reactions. CONCLUSION: S. aureus outbreaks are commonly associated with colonization of healthcare workers, and are challenging to manage within environments such as neonatal units. This study highlights the utility of whole-genome sequencing in identifying and mapping an outbreak. It is recommended that targeted staff screening should be considered early in similar outbreaks. In this setting, mass suppression therapy was not an effective strategy despite a high level of staff engagement and compliance.

Planning to halve Gram-negative bloodstream infection: getting to grips with healthcare-associated Escherichia coli bloodstream infection sources.

BACKGROUND: A thorough understanding of the local sources, risks, and antibiotic resistance for Escherichia coli bloodstream infection (BSI) is required to focus prevention initiatives and therapy. AIM: To review the sources and antibiotic resistance of healthcare-associated E. coli BSI. METHODS: Sources and antibiotic resistance profiles of all 250 healthcare-associated (post 48 h) E. coli BSIs that occurred within our secondary and tertiary care hospital group from April 2014 to March 2017 were reviewed. Epidemiological associations with urinary source, gastrointestinal source, and febrile neutropenia-related BSIs were analysed using univariable and multivariable binary logistic regression models. FINDINGS: E. coli BSIs increased 9% from 4.0 to 4.4 per 10,000 admissions comparing the 2014/15 and 2016/17 financial years. Eighty-nine cases (36%) had a urinary source; 30 (34%) of these were classified as urinary catheter-associated urinary tract infections (UTIs). Forty-five (18%) were related to febrile neutropenia, and 38 (15%) had a gastrointestinal source. Cases were rarely associated with surgical procedures (11, 4%) or indwelling vascular devices (seven, 3%). Female gender (odds ratio: 2.3; 95% confidence interval: 1.2-4.6) and older age (1.02; 1.00-1.05) were significantly associated with a urinary source. No significant associations were identified for gastrointestinal source or febrile neutropenia-related BSIs. Forty-seven percent of the isolates were resistant to ciprofloxacin, 37% to third-generation cephalosporins, and 22% to gentamicin. CONCLUSION: The gastrointestinal tract and febrile neutropenia together accounted for one-third of E. coli BSI locally but were rare associations nationally. These sources need to be targeted locally to reduce an increasing trend of E. coli BSIs.

Evaluating serial screening cultures to detect carbapenemase-producing Enterobacteriaceae following hospital admission.

BACKGROUND: Carbapenem-producing Enterobacteriaceae (CPE) are on the rise worldwide. National guidelines for the prevention and control of CPE recommend screening for the detection of asymptomatic carriers on admission. AIM: To evaluate the benefit of serial screens for detecting the carriage of CPE and other antibiotic-resistant Gram-negative bacteria following hospital admission. METHODS: All CPE screens, which were cultured on chromogenic media and the presence of a carbapenemase confirmed by polymerase chain reaction, were analysed for a six-month period. National guidelines in England recommend three serial screens for CPE separated by 48 h for admission screening for 'at-risk' patients, during which the patient is isolated. Two screening scenarios were tested. In scenario A, patients received three screens at the specified timepoints, in line with English national guidelines; in scenario B, patients received three consecutive screens, but not necessarily within the specified timepoints, during one admission. General linear models or conditional logistic regression were used to detect any significant change in the rate of carriage. FINDINGS: There was no significant increase in the detected carriage rate of CPE across any of the three timepoints in the scenarios tested. However, there was a significant increase in the detected rate of carriage of Gram-negative bacteria, Enterobacteriaceae, and resistant Enterobacteriaceae (excluding CPE) in scenario B. CONCLUSION: Three serial screens were not useful for the detection of CPE carriage on admission. The increase in the carriage rate of other Gram-negative bacteria may be explained by 'unmasking' of pre-existing carriage, or acquisition. This argues for regular screening of long-stay patients.

Counting the cost of an outbreak of carbapenemase-producing Enterobacteriaceae: an economic evaluation from a hospital perspective.

OBJECTIVE: To perform an economic evaluation on the cost associated with an outbreak of carbapenemase-producing Enterobacteriaceae (CPE). METHODS: We performed an observational economic evaluation of an outbreak of CPE (NDM-producing Klebsiella pneumoniae) affecting 40 patients in a group of five hospitals across three sites in West London. Costs were split into actual expenditure (including anti-infective costs, enhanced CPE screening, contact precautions, temporary ward-based monitors of hand and environmental practice, and environmental decontamination), and 'opportunity cost' (staff time, bed closures and elective surgical missed revenue). Costs are estimated from the hospital perspective over the 10-month duration of the outbreak. RESULTS: The outbreak cost €1.1m over 10 months (range €0.9-1.4m), comprising €312 000 actual expenditure, and €822 000 (range €631 000-€1.1m) in opportunity cost. An additional €153 000 was spent on Estates renovations prompted by the outbreak. Actual expenditure comprised: €54 000 on anti-infectives for 18 patients treated, €94 000 on laboratory costs for screening, €73 000 on contact precautions for 1831 contact precautions patient-days, €42 000 for hydrogen peroxide vapour decontamination of 24 single rooms, €43 000 on 2592 hours of ward-based monitors, and €6000 of expenditure related to ward and bay closures. Opportunity costs comprised: €244 000 related to 1206 lost bed-days (range 366-2562 bed-days, €77 000-€512 000), €349 000 in missed revenue from 72 elective surgical procedures, and €228 000 in staff time (range €205 000-€251 000). Reduced capacity to perform elective surgical procedures related to bed closures (€349 000) represented the greatest cost. CONCLUSIONS: The cost estimates that we present suggest that CPE outbreaks are highly costly.

Isolation demand from carbapenemase-producing Enterobacteriaceae screening strategies based on a West London hospital network.

OBJECTIVE: To estimate the isolation demands arising from high-risk specialty-based screening for carbapenemase-producing Enterobacteriaceae (CPE), and the potential fraction of CPE burden detected. METHODS: Clinical specialty groups from three London hospitals were ranked by incidence of carbapenem resistance among Escherichia coli and Klebsiella spp. Contact precaution bed-days were estimated for three screening strategies: Strategy 1, 'circulation science and renal medicine'; Strategy 2, Strategy 1 plus 'specialist services'; and Strategy 3, Strategy 2 plus 'private patients'. Isolation bed occupancy rates and potential CPE detection rates were estimated. RESULTS: Of 99,105 admissions to the three hospitals in Financial Year 2014/15, Strategies 1, 2 and 3 would have screened 4371 (4.4%), 7482 (7.6%), and 13,542 (13.7%) patients, respectively. The specialties' isolation bed occupancy rates varied between 3% and 696% depending on strategy, number of consecutive tests, and whether or not pre-emptive isolation had been applied. Expected detection rates of the potential CPE burden in the hospital network would have varied between 17.1% and 47.5%. CONCLUSIONS: High-risk specialty-based screening has the potential to detect nearly half of the potential CPE burden, and would be more pragmatic than patient-level risk-factor-based screening. Pre-emptive isolation increases isolation requirements substantially. CPE screening strategies need to balance risk and resources.

Forecasting carbapenem resistance from antimicrobial consumption surveillance: Lessons learnt from an OXA-48-producing Klebsiella pneumoniae outbreak in a West London renal unit.

This study aimed to forecast the incidence rate of carbapenem resistance and to assess the impact of an antimicrobial stewardship intervention using routine antimicrobial consumption surveillance data. Following an outbreak of OXA-48-producing Klebsiella pneumoniae (January 2008-April 2010) in a renal cohort in London, a forecasting ARIMA model was derived using meropenem consumption data [defined daily dose per 100 occupied bed-days (DDD/100OBD)] from 2005-2014 as a predictor of the incidence rate of OXA-48-producing organisms (number of new cases/year/100,000OBD). Interrupted times series assessed the impact of meropenem consumption restriction as part of the outbreak control. Meropenem consumption at lag -1 year (the preceding year), highly correlated with the incidence of OXA-48-producing organisms (r=0.71; P=0.005), was included as a predictor within the forecasting model. The number of cases/100,000OBD for 2014-2015 was estimated to be 4.96 (95% CI 2.53-7.39). Analysis of meropenem consumption pre- and post-intervention demonstrated an increase of 7.12 DDD/100OBD/year (95% CI 2.97-11.27; P<0.001) in the 4 years preceding the intervention, but a decrease thereafter. The change in slope was -9.11 DDD/100OBD/year (95% CI -13.82 to -4.39). Analysis of alternative antimicrobials showed a significant increase in amikacin consumption post-intervention from 0.54 to 3.41 DDD/100OBD/year (slope +0.72, 95% CI 0.29-1.15; P=0.01). Total antimicrobials significantly decreased from 176.21 to 126.24 DDD/100OBD/year (P=0.05). Surveillance of routinely collected antimicrobial consumption data may provide a key warning indicator to anticipate increased incidence of carbapenem-resistant organisms. Further validation using real-time data is needed.

An analysis of the development and implementation of a smartphone application for the delivery of antimicrobial prescribing policy: lessons learnt.

OBJECTIVES: Smartphone usage amongst clinicians is widespread. Yet smartphones are not widely used for the dissemination of policy or as clinical decision support systems. We report here on the development, adoption and implementation process of the Imperial Antimicrobial Prescribing Application across five teaching hospitals in London. METHODS: Doctors and clinical pharmacists were recruited to this study, which employed a mixed methods in-depth case-study design with focus groups, structured pre- and post-intervention survey questionnaires and live data on application uptake. The primary outcome measure was uptake of the application by doctors and its acceptability. The development and implementation processes were also mapped. RESULTS: The application was downloaded by 40% (376) of junior doctors with smartphones (primary target user group) within the first month and by 100% within 12 months. There was an average of 1900 individual access sessions per month, compared with 221 hits on the Intranet version of the policy. Clinicians (71%) reported that using the application improved their antibiotic knowledge. CONCLUSIONS: Clinicians rapidly adopted the mobile application for antimicrobial prescribing at the point of care, enabling the policy to reach a much wider audience in comparison with paper- and desktop-based versions of the policy. Organizations seeking to optimize antimicrobial prescribing should consider utilizing mobile technology to deliver point-of-care decision support. The process revealed a series of barriers, which will need to be addressed at individual and organizational levels to ensure safe and high-quality delivery of local policy at the point of care.

Prevalence of healthcare device-associated infection using point prevalence surveys of antimicrobial prescribing and existing electronic data.

This study extended a previously described method for the prevalence of healthcare-associated infection, based on point prevalence surveys of antimicrobial prescribing and electronic data, to estimate the prevalence of device-associated infections. In June 2009, the six-month point prevalence survey of antimicrobial prescribing was carried out in accordance with the European Surveillance of Antimicrobial Consumption Protocol. For patients receiving antimicrobials the presence of devices was recorded. A census on device use was carried out concurrently in the relevant hospitals. We selected patients receiving antimicrobials, started >48h after admission and who had a device, or who were without a device but were receiving antimicrobials for the treatment of bloodstream infection, urinary tract infection, or pneumonia. From existing positive microbiological and radiology reports, these patients were assessed for the presence of device-associated infection according to specified definitions. Of 1354 patients surveyed, 253 (19%) were receiving antimicrobial for treatment; of these, 189 also had devices and 172 (only 13% of all patients surveyed) needed individual assessment for the presence of device-associated infection. It took about 5min per patient to check electronic microbiology and/or radiology reports. Twenty-three patients met the criteria for device-associated infection. The prevalence of catheter-associated urinary tract infection, central-line-associated bloodstream infection, local vascular access infection, and ventilator-associated pneumonia was 3.9%, 3.1%, 3.8% and 11.6%, respectively. This is a simple method, which can be adopted in other hospitals, to estimate the prevalence of device-associated infection using pre-existing data.

Campylobacter jejuni cellulitis in a patient with pan-hypogammaglobulinaemia.

The case of a 17-year-old male with recurrent episodes of cellulitis affecting his left shin is presented. The cellulitis had been present on an intermittent basis over an 18-month period despite several courses of both intravenous and oral antibiotics. Each course of antibiotics resulted in a temporary remission, but on four occasions the cellulitis then relapsed. The patient was known to have pan-hypogammaglobulinaemia and was receiving intravenous IgG replacement therapy every 3 weeks. Other than cellulitis, he remained generally well. The organism responsible for the cellulitis was unknown until Campylobacter jejuni was grown in blood cultures during one of the relapse episodes. Based on microbial sensitivity, the patient was treated with ciprofloxacin. This resulted in full resolution of the cellulitis and he remains well. This case illustrates the value of blood cultures in helping microbial identification, particularly in immunocompromised patients with atypical infections.

Where does infection control fit into a hospital management structure?

To be effective, infection prevention and control must be integrated into the complex and multiple interlinking systems within a hospital's management structure. Each of the systems must consider how activity associated with it can be optimised to minimise infection risk to patients. The components of an organisational structure to achieve these quality assurance and patient safety aims are discussed. The use of performance management tools in relation to infection control metrics is reviewed, and the use of hospital-acquired infection as a proxy indicator for deficiencies of system management is considered. Infection prevention and control cannot be the role and responsibility of a single individual or a small dedicated team; rather it should be a priority at all levels and integrated within all management systems, including the research and educational agendas.

Impact of the use of aminoglycosides in combination antibiotic therapy on septic shock and mortality due to Staphylococcus aureus bacteremia.

BACKGROUND: The purpose of this study was to evaluate the possible impact of antimicrobial combination regimens containing an aminoglycoside (AG) on morbidity and mortality associated with S. aureus bacteremia. METHODS: All inpatients over 18 years of age with S. aureus bacteremia were prospectively enrolled in three tertiary care hospitals in France and Ireland. Patients were included in the group "treated with AG" if they received at least 24 h of aminoglycoside therapy within 7 days after a positive blood culture in combination with an effective antimicrobial against the S. aureus. A Cox's proportional hazard model was used in univariate and multivariate survival analysis, the covariate "treatment with AG" being introduced as a time-dependent covariate. RESULTS: Nine percent of the 90 patients who received AG died because of infection versus 13% in the group that did not receive a combination including an AG (p>0.05). In the multivariate Cox model, stratified by septic shock and controlling for age and Charlson-weighted index of comorbidity, the adjusted odds ratio for death due to S. aureus infection associated with the use of AG was 0.6 [95% CI: (0.2-1.9); p=0.4]. However, AG was found to have a protective effect on septic shock occurrence [OR=0.3; 95% CI: (0.1-0.7), p=0.004], controlling for age, portal of entry not related to catheter infection, and diabetes. CONCLUSION: Although there was no decrease in mortality due to S. aureus infection in patients treated with AG therapy, we found a significant benefit of AG in preventing septic shock. This data argues for the early use of AG in patients with S. aureus bacteremia.

Positive surveillance blood culture is a predictive factor for secondary metastatic infection in patients with Staphylococcus aureus bacteraemia.

PURPOSE: Staphylococcus aureus bacteraemia (SAB) may be complicated by secondary metastatic infection such as endocarditis, osteomyelitis or septic arthritis. This cohort study aimed to assess the prognostic value of sustained bacteraemia for outcomes related to Staphylococcus aureus bacteraemia. SUBJECTS AND METHODS: The study took place in three tertiary-care, university-affiliated hospitals. Patients were prospectively included if they agreed to participate and if the following data were available: (a). surveillance blood culture taken between 24 and 48 h after commencement of effective antibiotic therapy; (b). appropriate investigations (at least a TTE) performed as suggested by the infectious diseases consult service. Patients with sustained bacteraemia defined as persistent positive blood cultures more than 24 h after commencement of effective antibiotic therapy were compared to patients for whom the surveillance blood culture was negative. RESULTS: One hundred and four patients were enrolled, including 51 patients diagnosed with sustained bacteraemia. Sustained bacteraemia was significantly associated with a higher frequency of secondary metastatic infection (p<0.001) and with a higher frequency of CRP>100 mg/l. Frequency of acute complications due to infection, septic shock and death due to bacteraemia was higher for patients with sustained bacteraemia but this difference was not statistically significant. Using a Cox model, the risk for death associated with sustained SAB, controlling for Index of comorbidity and age (categorised asor=70 years), was 1.2 (95% CI: (0.5, 3); p>0.05). CONCLUSION: In conclusion, surveillance blood cultures, especially performed on effective antibiotic therapy, may be a simple and cost-effective way to select a population at risk for secondary metastatic infection from SAB.