JAC Advance Access originally published online on January 31, 2008
Journal of Antimicrobial Chemotherapy 2008 61(3):743-745; doi:10.1093/jac/dkm543
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Original research |
Antimicrobial policies in the neonatal units of the United Kingdom and Republic of Ireland
1 Division of Child Health, St George’s, University of London, Cranmer Terrace, London SW17 0RE, UK 2 Evelina Children’s Hospital at St Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, UK
* Corresponding author. Tel: +44-20-7188-4679; Fax: +44-20-7188-4612; E-mail: esse.menson{at}gstt.nhs.uk
Received 17 October 2007; returned 27 November 2007; revised 15 November 2007; accepted 17 December 2007
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Abstract |
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Objectives: To review antibiotic and antifungal policies in British and Irish neonatal units (NNUs).
Methods: A telephone survey was performed regarding empirical antimicrobial guidelines of NNUs in the UK and Republic of Ireland.
Results: The response rate was 91% (202 of 222 NNUs). The guidelines from all responding units covered group B Streptococcus and Escherichia coli, the most common causes of neonatal septicaemia and meningitis. However, 19% did not cover Listeria, the cause of meningitis in 5% to 7% of cases in England and Wales. Second-line recommendations varied greatly between units, with widespread use of broad-spectrum agents. Fungal prophylaxis and treatment guidelines were generally rudimentary.
Conclusions: Empirical antimicrobial recommendations on many NNUs include broad-spectrum antibiotics without ensuring universal coverage of important pathogens. We raise concerns about the selection pressures exerted for resistant pathogens and invasive fungal disease, especially as few units specify fungal prophylaxis or treatment guidance. Development of rational guidelines for the UK and Irish neonatal units might help to optimize treatment while minimizing overuse of broad-spectrum agents.
Keywords: neonatal infection , antimicrobial agents , guidelines
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Introduction |
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Antimicrobials are essential to help minimize mortality and morbidity from neonatal infection, yet judicious selection of agents is required if appropriate pathogen coverage is to be achieved without providing the selection pressure for antibiotic-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and fungi. Prompted by a fatal case of early onset neonatal listeriosis, we surveyed antimicrobial guidelines in all neonatal units (NNUs) in the UK and Republic of Ireland in order to evaluate current empirical recommendations. We report the first study to provide a snapshot of current antibiotic policies in British and Irish NNUs.
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Methods |
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We carried out a telephone audit of all NNUs in the UK and Republic of Ireland between February 2006 and February 2007. Units were identified from The Directory of Critical Care (CMA Medical Data, 2005). Of the 229 units listed, 6 had closed and 1 was excluded because it was a highly specialized NNU without attached obstetric facilities. Consent was obtained from senior medical or nursing staff at each unit. A team member was asked to refer to their unit guidelines in order to report unit policy on empirical antimicrobial recommendations for specific clinical scenarios. Ethical approval was not sought as the study was a service evaluation not research.
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Results |
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We obtained data from 202 of 222 NNUs in the UK and Republic of Ireland (91%).
The source of antimicrobial dosing was published guidelines (e.g. Children’s British National Formulary) in 69% of NNUs. The remainder used local guidelines, among which dosing varied widely, e.g. benzylpenicillin from 25 to 100 mg/kg/dose, twice to four times daily.
First-line policies for early onset (EO) sepsis
Sixty-nine per cent of NNUs (140) recommended benzylpenicillin and gentamicin. A penicillin was not included in the first-line recommendation of 10% of NNUs (20) and 15% of post-natal wards (PNWs) (31), so failed to cover for Listeria monocytogenes. Furthermore, 4% of NNUs (8) and 5% of PNWs (11) did not specify the inclusion of a penicillin when the history might be suggestive of Listeria. Conversely, over half of the NNUs (117; 58%) recommended modifications to optimize cover for listeriosis when suspected (inclusion of ampicillin, amoxicillin or co-amoxiclav).
Twenty per cent of NNUs (41) advised empirical use of a cephalosporin (as monotherapy in 19 units) (Table 1). NNUs providing lower level intervention (level 1 units) and PNWs were more likely to recommend cephalosporins in first-line therapy: 37% of level 1 units (17/46), 26% of PNWs (53/203; 10 units as monotherapy), 20% of level 2 units (20/98) and 7% of level 3 units (4/58) (
2, P < 0.001).
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Second-line policies for EO sepsis
Of 75% of NNU policies (151) that advised empirical change of antibiotics for cases that failed to respond to first-line therapy, 49% (74) recommended cephalosporins second-line and 18% (27) recommended vancomycin.
Empirical antibiotic therapy for suspected meningitis
Nearly half of the NNU's empirical meningitis regimens included a cephalosporin (45%, 90), while a fifth did not use a penicillin-containing regimen (19%, 39). In 12% (25), the cephalosporin was monotherapy. A triple combination for suspected meningitis was advised in 5% (11) of NNUs (a cephalosporin plus a penicillin plus an aminoglycoside).
Eighty-nine per cent of NNUs stated an empirical first-line antibiotics regimen for LO sepsis (180); recommendations varied widely but in over a quarter (28%, 56 units), this was a broad-spectrum antibiotic (e.g. cephalosporin).
Empirical second-line policies for LO sepsis, reported from 46% of NNUs (93), varied even more widely, with the most common regimen (cefotaxime and vancomycin) accounting for only 8% and other recommendations including meropenem, teicoplanin, piperacillin/tazobactam and aztreonam.
Over one-third of the NNU policies (37%; 74 units) specified alternative antibiotics first-line for septic episodes where central venous catheters were in situ, most commonly vancomycin (21%) or teicoplanin (12%).
Guidance for use of antifungal prophylaxis was specified in only one-third of NNUs (32%; 64), but twice as many specified indications for antifungal treatment (65%; 131). Fluconazole and amphotericin were recommended equally (66 and 65 U, respectively).
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Discussion |
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Rational antibiotic policies for neonatal sepsis should cover the common and important pathogens, ideally guided by local, regional and national epidemiology, but British and Irish NNUs currently lack systematic neonatal infection surveillance. In the absence of this evidence base, we have examined units’ antimicrobial recommendations on the grounds that such policies are in place to direct empirical antimicrobial prescribing. To our knowledge, this study provides the first snapshot of current antimicrobial policies in UK and Irish NNUs.
While it is reassuring that empirical recommendations universally cover for group B Streptococcus (the commonest cause of neonatal septicaemia and meningitis) and susceptible strains of Escherichia coli, 1 in 10 NNUs do not cover the rarer but important pathogen L. monocytogenes when treating neonatal septicaemia empirically, and almost 1 in 5 (19%) do not cover for this organism when empirically treating neonatal meningitis. This is concerning in the light of the most recent data indicating that L. monocytogenes causes 5% to 7% of neonatal meningitis cases,1 and data on neonatal meningitis in England and Wales 10 years apart (1985–87 and 1996–97) show little change in the bacterial causes of neonatal meningitis.
In the UK as elsewhere, the rising incidence of MRSA in the paediatric population is centred largely in NNUs, and the experience of widespread MRSA infections in Japanese NNUs in the late 1980s is attributed in part to the overuse of broad-spectrum antibiotics.2 Use of third-generation cephalosporins is also associated with invasive fungal infections from which mortality is high.3 We therefore question the appropriateness of recommending broad-spectrum antibiotics such as cephalosporins widely. The reasons behind individual antibiotic policies were outside the scope of this study but, anecdotally, many units use third-generation cephalosporins because of real or perceived problems with aminoglycosides, including difficulties in obtaining timely drug-level results. National neonatal guidelines promoting the use of narrower spectrum antibiotics might encourage hospitals to provide therapeutic drug monitoring services routinely to NNUs. In addition, the need for therapeutic drug monitoring would be minimized by adherence to policies regarding the prompt cessation of antibiotics when cultures fail to grow pathogens (as monitoring is not required routinely until aminoglycosides are used for >48 h).4 Commonly recommending vancomycin for LO and line-related sepsis is also questioned given the high incidence but low morbidity and mortality from coagulase-negative Staphylococcus sepsis. We support the assertion from a Canadian study that vancomycin could be reserved for episodes in which the implicated organism is confirmed to be resistant to penicillins.5
We propose the development of guidelines for empirical treatment of common and important neonatal infections to promote narrower spectrum antibiotic regimens such as an aminoglycoside combined with benzylpenicillin for EO neonatal sepsis, or with flucloxacillin or amoxicillin for LO sepsis. Recommendations for prophylaxis and treatment of neonatal fungaemia would further assist in managing high-risk neonates.3 Guidelines underpinned by epidemiological data gathered by active, neonatologist-led, systematic neonatal infection surveillance should overcome the problems of knowledge and application of antibiotic policies that have been experienced elsewhere.6 Future studies would usefully evaluate actual practice and adherence to recommendations of antimicrobial choice and duration, particularly in the context of negative versus positive culture results and epidemiology.
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Funding |
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None to declare.
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Transparency declarations |
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TopAbstractIntroductionMethodsResultsDiscussionFundingTransparency declarationsReferences |
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None to declare.
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Acknowledgements |
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Our thanks are extended to Drs Mercedes A. Munteanu, Shahinul I. Khan and Sarah Wilson for assistance in data collection. We also thank all the participating neonatal units.
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References |
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1 Heath PT, Nik Yusoff NK, Baker CJ. Neonatal meningitis. Arch Dis Child Fetal Neonatal Ed (2003) 88:F173–8.
2 Fernando AMR, McQueen S, Sharland M. Coping with MRSA. Curr Paediatr (2005) 15:437–42.[CrossRef]
3
Manzoni P, Farina D, Leonessa M-L, et al. Risk factors for progression to invasive fungal infection in preterm neonates with fungal colonization. Pediatrics (2006) 118:2359–64.
4 Hansen A, Forbes P, Arnold A, et al. Once-daily gentamicin dosing for the preterm and term newborn: proposal for a simple regimen that achieves target levels. J Perinatol (2003) 23:635–9.[CrossRef][Medline]
5 Lawrence SL, Roth V, Slinger R, et al. Cloxacillin versus vancomycin for presumed late-onset sepsis in the Neonatal Intensive Care Unit and the impact upon outcome of coagulase negative staphylococcal bacteremia: a retrospective cohort study. BMC Pediatr (2005) 5:49.[CrossRef][Medline]
6 Alexandre-Treilles M, Chenaud M, Kacet N, et al. Pediatric management of early-onset neonatal sepsis: guidelines adherence in Lille’s perinatal care network. Arch Pediatr (2006) 13:341–5.[CrossRef][Web of Science][Medline]
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