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Genomic medicine steps closer to the clinic
Editorial
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Management of early neonatal infections: a work in progress
For the NICE guideline see http:// guidance.nice.org.uk/CG149
Worldwide, more than 3 million neonatal deaths were attributed to infections in 2010, some 40% of the total deaths in children younger than 5 years. Protecting life in its perilous first 72 h is important in the race to attain MDG 4, which calls for childhood mortality to be reduced by two thirds between 1990 and 2015. Yet, in the UK one in four diagnosed early-onset neonatal infections culminates in death, despite treatments and care pathways that should be well honed. There is also substantial morbidity, with infections a particular risk in premature and low birthweight newborn babies. Perceiving unacceptable variations in diagnosis and treatment of early-onset neonatal infections, the UK’s National Institute for Health and Clinical Excellence, NICE, has released a guideline seeking to clarify and unify best practice. The pathogens involved—group B streptococcus, Escherichia coli, and others—are known and common in delivery settings, and a first-line empirical antibiotic regimen of intravenous benzylpenicillin with gentamicin is well established. Conversely, there is a need
to avoid unnecessary antibiotic use to prevent possible adverse effects of treatment and minimise resistance. The new guideline emphasises risk factors for neonatal infections, including group B streptococcal infection in a previous baby; clinical indicators of possible infection, such as abnormal behaviour and respiratory distress more than 4 h post partum; initiating antibiotic treatment within 1 h of the decision to treat, supported by appropriate monitoring of blood or cerebrospinal fluid; and provision of support to parents, who should be involved in decisions about care when feasible. This NICE guideline will gain in complexity when applied against a background of evolving microbiology and a health system undergoing reorganisation. Proper training in maternity units will be crucial, and success will need to be judged by surveillance of processes and outcomes in early-onset neonatal infections in the NHS in future years. In the long term, research aimed at swifter identification of microorganisms and development of new targeted drug treatments should be a priority. The Lancet
Science Photo Library
Genomic medicine steps closer to the clinic
Klebsiella pneumoniae
For the research article see Sci Transl Med http://dx.doi. org/10.1126/scitranslmed.3004129
780
“Gene detectives find new tool to contain deadly bacteria” and “CSI Bethesda: Sleuths used sequenced genome to track down killer” were just some of the newspaper headlines sparked by an early online publication in Science Translational Medicine last week. The research article details a medical mystery that led to the novel tracking of a hospital outbreak of carbapenem-resistant Klebsiella pneumoniae with whole-genome sequencing. In July last year, the US National Institutes of Health (NIH) Clinical Center admitted a patient with carbapenemresistant K pneumoniae whose care included strict infection control measures such as isolation. The patient was eventually discharged after successful treatment. However, 3 weeks later a second case of the drug-resistant bacterium emerged at the centre in a patient who had never been in the same location as the first. The outbreak continued over a 6 month period—18 patients were affected in total, 11 of whom died (six from the infection). To find out how transmission occurred, the NIH researchers used whole-genome sequencing to compare patients’ bacterial strains. Most strains of K pneumoniae
in the USA belong to the same clone and are difficult to distinguish with traditional methods such as pulsed field gel electrophoresis. However, sequencing revealed that despite the 3 week gap, the infection in the index patient had triggered the outbreak and transmission occurred from three different sites on the patient’s body. Tracking of the transmission using genomic and epidemiological data gave other insights, such as the emergence of colistin resistance, and led to broadened infection control efforts that eventually stopped the outbreak. The authors suggest that real-time application of this technology could guide hospital infection-control measures in the future. Although most hospitals do not yet have the resources to sequence bacterial genomes, the technology is rapidly becoming more affordable (from US$2000 per sequence in 2011 to $500 this year). Its use in controlling difficult hospital infections, such as K pneumoniae, certainly has the potential to become invaluable. The promise of genomic medicine has been a long time coming, but this latest research brings it tantalisingly close to reality. The Lancet www.thelancet.com Vol 380 September 1, 2012
Science Photo Library
Management of early neonatal infections: a work in progress
For the NICE guideline see http:// guidance.nice.org.uk/CG149
Worldwide, more than 3 million neonatal deaths were attributed to infections in 2010, some 40% of the total deaths in children younger than 5 years. Protecting life in its perilous first 72 h is important in the race to attain MDG 4, which calls for childhood mortality to be reduced by two thirds between 1990 and 2015. Yet, in the UK one in four diagnosed early-onset neonatal infections culminates in death, despite treatments and care pathways that should be well honed. There is also substantial morbidity, with infections a particular risk in premature and low birthweight newborn babies. Perceiving unacceptable variations in diagnosis and treatment of early-onset neonatal infections, the UK’s National Institute for Health and Clinical Excellence, NICE, has released a guideline seeking to clarify and unify best practice. The pathogens involved—group B streptococcus, Escherichia coli, and others—are known and common in delivery settings, and a first-line empirical antibiotic regimen of intravenous benzylpenicillin with gentamicin is well established. Conversely, there is a need
to avoid unnecessary antibiotic use to prevent possible adverse effects of treatment and minimise resistance. The new guideline emphasises risk factors for neonatal infections, including group B streptococcal infection in a previous baby; clinical indicators of possible infection, such as abnormal behaviour and respiratory distress more than 4 h post partum; initiating antibiotic treatment within 1 h of the decision to treat, supported by appropriate monitoring of blood or cerebrospinal fluid; and provision of support to parents, who should be involved in decisions about care when feasible. This NICE guideline will gain in complexity when applied against a background of evolving microbiology and a health system undergoing reorganisation. Proper training in maternity units will be crucial, and success will need to be judged by surveillance of processes and outcomes in early-onset neonatal infections in the NHS in future years. In the long term, research aimed at swifter identification of microorganisms and development of new targeted drug treatments should be a priority. The Lancet
Science Photo Library
Genomic medicine steps closer to the clinic
Klebsiella pneumoniae
For the research article see Sci Transl Med http://dx.doi. org/10.1126/scitranslmed.3004129
780
“Gene detectives find new tool to contain deadly bacteria” and “CSI Bethesda: Sleuths used sequenced genome to track down killer” were just some of the newspaper headlines sparked by an early online publication in Science Translational Medicine last week. The research article details a medical mystery that led to the novel tracking of a hospital outbreak of carbapenem-resistant Klebsiella pneumoniae with whole-genome sequencing. In July last year, the US National Institutes of Health (NIH) Clinical Center admitted a patient with carbapenemresistant K pneumoniae whose care included strict infection control measures such as isolation. The patient was eventually discharged after successful treatment. However, 3 weeks later a second case of the drug-resistant bacterium emerged at the centre in a patient who had never been in the same location as the first. The outbreak continued over a 6 month period—18 patients were affected in total, 11 of whom died (six from the infection). To find out how transmission occurred, the NIH researchers used whole-genome sequencing to compare patients’ bacterial strains. Most strains of K pneumoniae
in the USA belong to the same clone and are difficult to distinguish with traditional methods such as pulsed field gel electrophoresis. However, sequencing revealed that despite the 3 week gap, the infection in the index patient had triggered the outbreak and transmission occurred from three different sites on the patient’s body. Tracking of the transmission using genomic and epidemiological data gave other insights, such as the emergence of colistin resistance, and led to broadened infection control efforts that eventually stopped the outbreak. The authors suggest that real-time application of this technology could guide hospital infection-control measures in the future. Although most hospitals do not yet have the resources to sequence bacterial genomes, the technology is rapidly becoming more affordable (from US$2000 per sequence in 2011 to $500 this year). Its use in controlling difficult hospital infections, such as K pneumoniae, certainly has the potential to become invaluable. The promise of genomic medicine has been a long time coming, but this latest research brings it tantalisingly close to reality. The Lancet www.thelancet.com Vol 380 September 1, 2012