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The Scottish enhanced Staphylococcus aureus bacteraemia surveillance programme: the first 18 months of data in children

      Summary

      Background

      National enhanced surveillance of Staphylococcus aureus bacteraemia (SAB) commenced on 1st October 2014 to gain a more in-depth understanding of the epidemiology of SAB in Scotland. Children under 16 years of age were analysed separately from adults because previous studies had demonstrated epidemiological differences.

      Aim

      To identify risk factors and patient populations at greatest risk to enable the development of focused improvement plans.

      Methods

      All National Health Service (NHS) boards within NHS Scotland take part in the mandatory enhanced surveillance, with data collected by trained data collectors using nationally agreed definitions.

      Findings

      Analysis of the first 18 months of data showed that hospital-acquired SAB was mostly associated with neonates with device risk factors, whereas community-associated SAB was found in older children who had few, if any, risk factors and most presented with a bone or joint infection.

      Conclusion

      The enhanced SAB data highlighted the difference in risk factors and entry points for the acquisition of SAB within the paediatric population.

      Keywords

      Introduction

      Staphylococcus aureus is a major cause of hospital-acquired, healthcare-associated and community-acquired bacteraemia. The incidence, especially for hospital-acquired S. aureus bacteraemia (SAB), remains high, partly due to a high number of invasive methods of treatment including vascular access devices. SAB is a major problem in adult patients, with significant morbidity and mortality [
      • Yilmaz M.
      • Elaldi N.
      • Balkan II,
      • Arslan F.
      • Batırel A.A.
      • Bakıcı M.Z.
      • et al.
      Mortality predictors of Staphylococcus aureus bacteremia: a prospective multicenter study.
      ]. Little is known about SAB in the neonatal and paediatric population, especially regarding the main entry points and deep metastatic infections. This knowledge is essential for development of focused improvement plans, both locally and nationally, to reduce the burden of SAB in this patient population.
      The analysis of longer-term trends of published mandatory data in Scotland showed no significant increase or decrease in the total incidence of SAB in the last five years [
      • Health Protection Scotland
      The Staphylococcus aureus bacteraemia quarterly report of cumulative data from all NHS boards in Scotland.
      ]. However, there was a decrease in the number of patients with meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia and an increase in the number of patients with meticillin-sensitive S. aureus (MSSA) bacteraemia in Scotland. Data from other countries suggest that, in some centres, MRSA is increasing in frequency as a cause of SAB in children [
      • Mongkolrattanothai K.
      • Aldag J.C.
      • Mankin P.
      • Gray B.M.
      Epidemiology of community-onset Staphylococcus aureus infections in pediatric patients: an experience at a children's hospital in central Illinois.
      ]. In a study in Illinois, USA, Mongkolrattanothai et al. found that MRSA is increasing as a cause of skin and soft tissue infection in the community, but MSSA remains a common cause of invasive infections [
      • Mongkolrattanothai K.
      • Aldag J.C.
      • Mankin P.
      • Gray B.M.
      Epidemiology of community-onset Staphylococcus aureus infections in pediatric patients: an experience at a children's hospital in central Illinois.
      ].
      Historically, more than half of the SAB episodes in adults were hospital acquired [
      • Cunney R.J.
      • McNamara E.B.
      • Alansari N.
      • Smyth E.G.
      Community and hospital acquired Staphylococcus aureus septicaemia: 115 cases from a Dublin teaching hospital.
      ,
      • Maradona J.A.
      • Carton J.A.
      • Lopez-Alonso J.
      • Carcaba V.
      • Nuno F.J.
      • Arribas J.M.
      Comparative study of community versus hospital-acquired Staphylococcus aureus bacteraemia.
      ]. Mandatory surveillance data from England and Wales from the last decade of the 20th Century and the beginning of the 21st Century showed an overall increase in SAB rates, including SAB in children, with MRSA bacteraemia rates reported to be as high as 40% of the overall SAB [
      • Health Protection Agency
      The third year of regional and national analyses of the Department of Health's mandatory MRSA surveillance scheme in England: April 2001–March 2004.
      ,
      • Khairulddin N.
      • Bishop L.
      • Lamagni T.L.
      • Sharland M.
      • Duckworth G.
      Emergence of methicillin resistant Staphylococcus aureus (MRSA) bacteraemia among children in England and Wales, 1990–2001.
      ]. This led to development of numerous initiatives aiming to reduce healthcare-associated infections, and SAB rates became a national performance indicator for hospital-acquired infection, impinging on Commission for Health Improvement scores and hospital trust finances. All National Health Service (NHS) Boards in Scotland have been set a local delivery plan to achieve, and one of these targets is reduction of the number of SAB cases. This target, previously termed ‘Health Improvement, Efficiency, Access and Treatment’, was established in 2006 for SAB. Mandatory enhanced surveillance for SAB was established in NHS Scotland in October 2014 as a result of collaborative work of infection prevention and control teams (IPCTs) from the Scottish health boards and Health Protection Scotland (HPS).
      Previous studies on SAB in children indicated that disease severity differs between children and adult populations [
      • Chang F.Y.
      • MacDonald B.B.
      • Peacock Jr., J.E.
      • Musher D.M.
      • Triplett P.
      • Mylotte J.M.
      • et al.
      A prospective multicenter study of Staphylococcus aureus bacteremia: incidence of endocarditis, risk factors for mortality, and clinical impact of methicillin resistance.
      ,
      • Fowler Jr., V.G.
      • Olsen M.K.
      • Corey G.R.
      • Woods C.W.
      • Cabell C.H.
      • Reller L.B.
      • et al.
      Clinical identifiers of complicated Staphylococcus aureus bacteremia.
      ,
      • Mylotte J.M.
      • Tayara A.
      Staphylococcus aureus bacteremia: predictors of 30-day mortality in a large cohort.
      ]. Previous studies have also noted that MRSA is increasingly identified as a cause of bloodstream infection in children [
      • Khairulddin N.
      • Bishop L.
      • Lamagni T.L.
      • Sharland M.
      • Duckworth G.
      Emergence of methicillin resistant Staphylococcus aureus (MRSA) bacteraemia among children in England and Wales, 1990–2001.
      ,
      • Chuang Y.Y.
      • Huang Y.C.
      • Lee C.Y.
      • Lin T.Y.
      • Lien R.
      • Chou Y.H.
      Methicillin-resistant Staphylococcus aureus bacteraemia in neonatal intensive care units: an analysis of 90 episodes.
      ,
      • Gonzalez B.E.
      • Martinez-Aguilar G.
      • Hulten K.G.
      • Hammerman W.A.
      • Coss-Bu J.
      • Avalos-Mishaan A.
      • et al.
      Severe staphylococcal sepsis in adolescents in the era of community-acquired methicillin-resistant Staphylococcus aureus.
      ,
      • Healy C.M.
      • Palazzi D.L.
      • Edwards M.S.
      • Campbell J.R.
      • Baker C.J.
      Features of invasive staphylococcal disease in neonates.
      ,
      • Healy C.M.
      • Hulten K.G.
      • Palazzi D.L.
      • Campbell J.R.
      • Baker C.J.
      Emergence of new strains of methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit.
      ,
      • Isaacs D.
      • Fraser S.
      • Hogg G.
      • Li H.Y.
      Staphylococcus aureus infections in Australasian neonatal nurseries.
      ]. In adults, SAB carries both high morbidity and mortality of up to 30% [
      • Wyllie D.H.
      • Crook D.W.
      • Peto T.E.
      Mortality after Staphylococcus aureus bacteraemia in two hospitals in Oxfordshire, 1997–2003: cohort study.
      ]. Mortality in children with SAB appears to be lower despite the presence of significant underlying diseases, but can be up to 15% [
      • Hakim H.
      • Mylotte J.M.
      • Faden H.
      Morbidity and mortality of staphylococcal bacteremia in children.
      ,
      • Saunderson R.B.
      • Gouliouris T.
      • Cartwright E.J.
      • Nickerson E.J.
      • Aliyu S.H.
      • O'Donnell D.R.
      • et al.
      Impact of infectious diseases consultation on the management of Staphylococcus aureus bacteraemia in children.
      ].
      This paper will analyse the data collected from the paediatric population in the first 18 months of enhanced SAB surveillance in Scotland to demonstrate the individual patient risk factors that should be considered to prevent SAB in neonates and children.

      Methods

      Data collection

      Data were collected between 1st October 2014 and 31st March 2016 through the mandatory SAB surveillance programme [
      • Scottish Executive Health Department
      A revised framework for national surveillance of healthcare associated infection in Scotland.
      ,
      • Scottish Executive Health Department
      A framework for national surveillance of healthcare acquired infection in Scotland.
      ,
      • Scottish Government
      Healthcare associated infection (HAI) and antimicrobial resistance (AMR) policy requirements.
      ]. An episode of SAB was defined in the HPS SAB surveillance protocol as a positive blood culture for S. aureus with no positive S. aureus blood culture in the previous 14 days, excluding postmortem blood cultures [
      • Health Protection Scotland
      Protocol for the Scottish Mandatory Surveillance Programme for Staphylococcus aureus bacteraemia.
      ]. IPCT data collectors were trained using the Enhanced S. aureus Bacteraemia Surveillance Protocol [
      • Health Protection Scotland
      Protocol for enhanced Staphylococcus aureus bacteraemia surveillance.
      ], and collated information in an Excel (Microsoft Corp., Redmond, WA, USA) spreadsheet that was exported to the surveillance team at HPS at the end of each quarter.
      The enhanced data collected included demographic details, origin of infection, source of bacteraemia and risk factors. The origin of infection was divided into hospital-acquired infection (HAI), healthcare-associated infection (HCAI), community-acquired infection and not known using definitions modified from Morris and Russell [
      • Health Protection Scotland
      Protocol for enhanced Staphylococcus aureus bacteraemia surveillance.
      ,
      • Morris A.K.
      • Russell C.D.
      Enhanced surveillance of Staphylococcus aureus bacteraemia to identify targets for infection prevention.
      ]. Positive blood cultures that were considered to be contaminants were excluded from this study.
      The source field contained both entry point and sources of deep-seated/metastatic infection, and was mapped to provide the breakdown required for the analysis. Full details of the definitions are provided in HPS Protocol of Enhanced SAB surveillance [
      • Health Protection Scotland
      Protocol for enhanced Staphylococcus aureus bacteraemia surveillance.
      ]. Risk factors for invasive S. aureus infection were recorded. Data were collected on all devices in situ at the time of the first positive blood aspirate or present in the previous 30 days, but did not include devices inserted to treat the current SAB episode. Details were collected about skin integrity plus other risk factors, including previous hospital admission and immunosuppression [
      • Health Protection Scotland
      Protocol for enhanced Staphylococcus aureus bacteraemia surveillance.
      ]. More than one risk factor could be selected in any of the risk categories. A number of validation checks are performed by HPS every quarter to cross-check the definitions and risk factors selected.
      Outcomes of interest were 30-day all-cause mortality, and 30-day and 90-day re-admission after a positive SAB result. Outcome measures were calculated through linkage of the enhanced SAB data to National Records Scotland death records and SMR01 (Scottish Morbidity Recording) acute hospital episodes. Data were linked using the Community Health Index number.

      Data analysis

      Chi-squared tests were used to test differences in the distributions of sex, age groups, presence of device, skin or other risk factors, and entry point between the origin types. Logistic regression was used to estimate crude and adjusted odds ratios together with 95% confidence intervals for sex, age group, origin of infection, presence of device, skin or other risk factors, and entry point using SPSS Statistics Version 21.0 (IBM Corp., Armonk, NY, USA).

      Results

      Between 1st October 2014 and 31st March 2016, there were 137 episodes of SAB recorded in 135 neonates and children across 18 hospitals, three of which are specialist children's hospitals. In 13 episodes, the positive blood culture was deemed to be a contaminant so these samples were excluded from the study; 124 episodes were analysed. Of these, only four were MRSA (3.2%). No difference was found between males and females (P=0.889), and the median age was one year.
      The entry point was known in 58.9% (N=73) of cases, and 1.6% (N=2) of these had a metastatic deep focus. In 41.1% (N=51) of cases, the entry point was not identified but a deep focus was present in 58.8% (N=30) of cases. The most common known entry point recorded was vascular access device (VAD) (Table I). All device-related sources (VAD and device other than VAD) were responsible for 33.8% (N=42) of SAB cases in this patient population within NHS Scotland. VAD entry points included central venous catheter (CVC) (16.9%, N=21), peripherally inserted central catheter/midline (4.9%, N=6) and peripheral venous catheter (4.0%, N=5) (Figure 1). The most common (20.2%, N=25) metastatic deep focus was bone and joint infection (Table II).
      Table IPatient characteristics overall and by origin in 124 episodes of Staphylococcus aureus bacteraemia
      VariableTotal

      N=124
      CAI

      N=38 (30.6%)
      HCAI

      N=15 (12.1%)
      HAI

      N=71 (57.3%)
      P-value
      SexMale73 (58.9%)23 (60.5%)8 (53.3%)42 (59.2%)0.889
      Female51 (41.1%)15 (39.5%)7 (46.7%)29 (40.8%)
      AgeMedian (years)192<1
      <28 days42 (33.9%)5 (33.3%)37 (52.1%)<0.0001
      29 days –<12 months17 (13.7 %)2 (5.3%)1 (6.7%)14(19.7%)
      1–15 years65 (52.4%)36 (94.7%)9 (60.0%)20 (28.2%)
      SusceptibilityMRSA4 (3.2%)0 (0.0%)1 (6.7%)3 (4.2%)0.357
      MSSA120 (96.8%)38 (100%)14 (93.3%)68 (95.8%)
      Entry pointNot known/undefined51 (41.1%)31 (81.6%)3 (20.0%)17 (23.9%)<0.0001
      Other17 (13.7%)2 (5.3%)2 (13.3%)13 (18.3%)
      SSTI17 (13.7%)5 (13.2%)3 (20.0%)9 (12.7%)
      VAD39 (31.5%)7 (46.7%)32 (45.1%)
      Patient outcome30-day mortality3 (2.4%)3 (4.2%)0.317
      30-day re-admission18 (14.5%)5 (13.2%)13 (18.3%)0.180
      90-day re-admission28 (22.6%)5 (13.2%)23 (32.4%)0.006
      CAI, community-acquired infection; HCAI, healthcare-associated infection; HAI, hospital-acquired infection; MRSA; meticillin-resistant S. aureus; MSSA, meticillin-susceptible S. aureus; SSTI, skin and soft tissue infection; VAD, vascular access device.
      Figure 1
      Figure 1Breakdown of hospital-acquired infection and healthcare-associated infection device entry points. PVC, peripheral venous catheter; CVC, central venous catheter; PICC, peripherally inserted central catheter.
      Table IISource recorded as a deep-seated or metastatic infection
      Deep-seated infectionTotal

      N=124
      CAI

      N=38
      HCAI

      N=15
      HAI

      N=71
      Bone and joint infection25 (20.2%)24 (63.2%)1 (1.4%)
      Deep abscess/haematoma6 (4.8%)3 (7.9%)1 (6.7%)2 (2.8%)
      Implanted device1 (0.8%)1 (1.4%)
      CAI, community-acquired infection; HCAI, healthcare-associated infection; HAI, hospital-acquired infection.
      Table I details the association found between the entry points recorded and the origin of infection (P<0.001), highlighting the different entry points depending on the origin.

      Hospital-acquired infection

      HAI accounted for 57.3% (N=71) of SAB cases, with significantly more cases in neonatal patients under 28 days of age (52.1%, P<0.001). VADs accounted for 45.1% (N=32) of HAI cases, with CVCs being the most frequently recorded VAD entry point (Figure 1). Recorded risk factors indicated that most children had some form of device (Table III). The most commonly reported ‘other’ risk factor was related to medical intervention.
      Table IIIRisk factors by origin of Staphylococcus aureus bacteraemia
      VariableTotal

      N=124
      CAI

      N=38
      HCAI

      N=15
      HAI

      N=71
      Device risk factors
      Includes, but not exclusively: indwelling vascular access devices (VADs): (1) non-tunnelled central venous catheters (CVCs), tunnelled CVCs, dialysis lines, peripherally inserted central catheter lines, peripheral vascular catheters and fistulas; and (2) indwelling medical device other than VADs such as chest drains, surgical drains, tracheostomy, epidural anaesthetic devices, spinal anaesthetic devices, nephrostomy, urethral catheters, suprapubic catheters, self-catheterization and percutaneous endoscopic gastrostomy tubes, inserted in the 30 days prior to the date the positive blood culture was taken (applies to 1 and 2).
      73 (58.9%)10 (66.7%)63 (88.7%)
      Skin and soft tissue risk factors
      Includes, but not exclusively: infections of skin (pressure sores, trauma, ulcers, cuts, grazes, surgical incisions, burns and eczema), subcutaneous tissue, fascia and muscle (does not include deep-seated/metastatic soft tissue infection) that were present at the time the positive blood culture was taken.
      40 (32.3%)8 (21.1%)4 (26.7%)28 (39.4%)
      Other risk factors
      Includes, but not exclusively: medical/surgical instrumentation; intramuscular, intravenous, subcutaneous or intra-articular medication; venepuncture; immunosuppression; diabetes mellitus; previous hospital admission; or non-healthcare cosmetic procedure breaking skin or mucous membrane in the 30 days prior to the positive blood culture being taken.
      74 (59.7%)11 (73.3%)63 (88.7%)
      CAI, community-acquired infection; HCAI, healthcare-associated infection; HAI, hospital-acquired infection.
      a Includes, but not exclusively: indwelling vascular access devices (VADs): (1) non-tunnelled central venous catheters (CVCs), tunnelled CVCs, dialysis lines, peripherally inserted central catheter lines, peripheral vascular catheters and fistulas; and (2) indwelling medical device other than VADs such as chest drains, surgical drains, tracheostomy, epidural anaesthetic devices, spinal anaesthetic devices, nephrostomy, urethral catheters, suprapubic catheters, self-catheterization and percutaneous endoscopic gastrostomy tubes, inserted in the 30 days prior to the date the positive blood culture was taken (applies to 1 and 2).
      b Includes, but not exclusively: infections of skin (pressure sores, trauma, ulcers, cuts, grazes, surgical incisions, burns and eczema), subcutaneous tissue, fascia and muscle (does not include deep-seated/metastatic soft tissue infection) that were present at the time the positive blood culture was taken.
      c Includes, but not exclusively: medical/surgical instrumentation; intramuscular, intravenous, subcutaneous or intra-articular medication; venepuncture; immunosuppression; diabetes mellitus; previous hospital admission; or non-healthcare cosmetic procedure breaking skin or mucous membrane in the 30 days prior to the positive blood culture being taken.

      Healthcare-associated infection

      HCAI accounted for 12.1% (N=15) of SAB cases. VADs accounted for 46.7% (N=7) of HCAI cases. Risk factors were similar to HAI cases, with most children having some form of device listed or had had medical intervention in the previous 30 days.

      Community-acquired infection

      Community-acquired infection accounted for 30.6% (N=38) of SAB cases. All were MSSA and the median age of children was 9 years. The entry point was only recorded in 18.4% (N=7) of cases; however, a deep-seated/metastatic bone and joint infection was recorded in 63.2% (N=24) of cases. Deep-seated/metastatic infection was recorded more frequently in community-acquired cases (P<0.001). Only 21.1% (N=8) of children presented with any risk factors, all of which were skin and soft tissue risk factors.

      Outcomes of interest

      Patient all-cause 30-day mortality figures were low in this population (2.4%, N=3), and there were no deaths in the HCAI and community-acquired infection groups. Re-admission data at 90 days showed a difference (P=0.006), with 32.4% of HAI patients re-admitted in 90 days. The most common diagnosis of children being re-admitted was leukaemia.

      Discussion

      The introduction of enhanced SAB surveillance has allowed the identification of origin of infection and the associated risk factors. The data analysis has shown that risks and point of entry for SAB differ depending on the origin of the bacteraemia.
      Within the paediatric population, neonates present with some of the most complex medical conditions, and management often involves multiple invasive devices and procedures. These extrinsic risk factors coupled with reduced immune defences mean that bacteraemic infections have a significant negative effect on mortality and short-term morbidity within this patient population [
      • Garber S.J.
      • Puopolo K.M.
      Prevention of central line-associated bloodstream infections among infants in the neonatal intensive care unit.
      ]. The data show that the majority of SAB cases in the neonatal population were HAI; however, there was no significant relationship between 30-day mortality and origin.
      Skin and soft tissue risk factors were found in 21% of community-acquired infections compared with 39% of HAI. This demonstrates the importance of managing skin conditions in the paediatric population to aid the function of skin as a protective barrier, preventing entry of the pathogens. The importance of this finding should be highlighted as the skin of neonates (and infants) differs quite significantly from adult skin, and undergoes further development in the first year of life [
      • Stamatas G.N.
      • Nikolovski J.
      • Luedtke M.A.
      • Kollias N.
      • Wiegand B.C.
      Infant skin microstructure assessed in vivo differs from adult skin in organization and at the cellular level.
      ]. This is one of the important factors contributing to higher risk of infection in the paediatric population [
      • Forlin E.
      • Milani C.
      Sequelae of septic arthritis of the hip in children: a new classification and a review of 41 hips.
      ], and coupled with the usage of invasive devices, the additional compromise of the skin's protective function increases even further along with the risk of systemic infection.
      The data show that the majority of HAI and HCAI cases had device risk factors (88.7% and 66.7%, respectively), and neonates were represented more often in the HAI group. Neonatal units should consider the monitoring of invasive device practices for insertion and management. The implementation of care bundles can be used to monitor outcomes and focuses for improvement. Local units should be encouraged to record device days to allow enhanced data collection to provide further intelligence that can be used as a tool for improvement. Care bundles must be applied uniformly and at all times. It seems a paradox that this study found that CVC tunnelled lines are the most common entry point for HAI and HCAI SABs in children. Further investigation to establish the use of tunnelled vs non-tunnelled lines in this patient population is required.
      Analysis of the data highlighted that the vast majority (81.6%) of SAB cases acquired in the community had no entry point recorded. At the same time, over 60% of these cases had bone and joint infection recorded as a deep-seated or metastatic infection. It will be valuable to understand if data are missing due to incomplete clinical history documentation, or if other risk factors in children are required within the enhanced SAB surveillance data set. This needs further investigation as bone and joint infection in the paediatric population is an orthopaedic emergency, requiring prompt diagnosis and treatment. Infections of the musculoskeletal system in children can not only result in systemic acute infection (including SAB), but may also have significant consequences with regards to irreversible altered bone growth and lifelong adverse outcomes, with Staphylococcus aureus being the most common pathogen of septic arthritis and haematogenous osteomyelitis in the paediatric population [
      • Forlin E.
      • Milani C.
      Sequelae of septic arthritis of the hip in children: a new classification and a review of 41 hips.
      ,
      • Choi I.H.
      • Shin Y.W.
      • Chung C.Y.
      • Cho T.J.
      • Yoo W.J.
      • Lee D.Y.
      Surgical treatment of the severe sequelae of infantile septic arthritis of the hip.
      ,
      • Goergens E.D.
      • McEvoy A.
      • Watson M.
      • Barrett I.R.
      Acute osteomyelitis and septic arthritis in children.
      ].
      The national SAB surveillance in Scotland is being developed to allow hospital and speciality level analysis that will support clinical teams within this patient population to identify local clusters or trends.
      In conclusion, the first 18 months of analysis have highlighted the difference in risk factors and entry points for the acquisition of SAB within the paediatric population in Scottish children. Cases under the age of 1 year are more likely to be associated with hospital care and have venous access as a recorded risk factor, whereas cases aged 1–15 years are more likely to be community associated with few risk factors. The majority of cases in the older age group had unknown entry points and had bone or joint infection present at the time of presentation with SAB.
      Within the paediatric population, different improvement interventions need to be considered depending on the age group as sources of infection differ; the majority of cases occur in younger children in neonatal settings and relate to VAD. Care bundles and vascular access improvement plans should be used in neonatal treatment centres. General practitioners and accident and emergency departments should remain very vigilant for older children presenting with bone or joint pain, as septic arthritis and osteomyelitis is an orthopaedic emergency, and diagnosis and treatment must not be delayed. Therefore, all neonatal and paediatric patients presenting with SAB should be assessed for deep infection.

      Acknowledgements

      The authors wish to thank the Enhanced S. aureus Bacteraemia Short Life Working Group for the development of national definitions, protocols and implementation, and local surveillance teams for supplying the data used in this analysis.

      Conflict of interest statement

      None declared.

      Funding source

      None.

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