Katherine L. Henderson

Empirical treatment of neonatal sepsis: are the current guidelines adequate?

Objectives To use national laboratory surveillance data to determine whether pathogens responsible for neonatal bacteraemia were sensitive to nationally recommended antibiotic regimens. Design All reports of neonatal bacteraemia received by the Health Protection Agencys voluntary surveillance scheme in England and Wales from January 2006 until March 2008, were extracted from the database. Organisms were ranked by frequency, and proportions susceptible to antimicrobials recommended for empirical treatment of neonatal sepsis were determined. Results There were 1516 reports of bacteraemia for neonates <48 h old (early-onset) and 3482 reports for neonates 2–28 days old (late-onset). For early-onset bacteraemia, group B streptococcus (GBS) was the most frequent pathogen (31%) followed by coagulase-negative staphylococci (CoNS; 22%), non-pyogenic streptococci (9%) and Escherichia coli (9%). For late-onset bacteraemia, CoNS were isolated most frequently (45%), followed by Staphylococcus aureus (13%), Enterobacteriaceae (9%), E coli (7%) and GBS (7%). More than 94% of organisms (early-onset) were susceptible to regimens involving combinations of penicillin with either gentamicin or amoxicillin, amoxicillin combined with cefotaxime or cefotaxime monotherapy. More than 95% of organisms (late-onset) were susceptible to gentamicin with either flucloxacillin or amoxicillin and amoxicillin with cefotaxime, but only 79% were susceptible to cefotaxime monotherapy. Conclusions Current guidelines for empirical therapy in neonates with sepsis are appropriate. However, gentamicin-based regimens should be used in preference to cefotaxime-based treatments, because of lower levels of susceptibility to cefotaxime and the need to avoid exerting selective pressure for resistance. Surveillance data linked to clinical data should further inform rational antibiotic prescribing in neonatal units.

Decline of EMRSA-16 amongst methicillin-resistant Staphylococcus aureus causing bacteraemias in the UK between 2001 and 2007

OBJECTIVES Between 1998 and 2000, 95.6% of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemias in the UK were due to two epidemic strains, namely EMRSA-15 or EMRSA-16 (60.2% and 35.4%, respectively). We sought to determine the proportions of these strains before and after the general decline in MRSA bacteraemia that began around 2004. METHODS Consecutive MRSA isolates collected in 2001, 2003, 2005 and 2007 by the BSAC Bacteraemia Surveillance Programme were categorized to multilocus sequence typing (MLST) clonal complex and to SCCmec type by PCR. MICs were determined by the BSAC method. Data trends were tested for significance using a generalized linear regression model. RESULTS Collectively, EMRSA-15 and EMRSA-16 consistently accounted for approximately 95% of MRSA studied between 2001 and 2007, but the proportions of EMRSA-16 declined from 21.4% in 2001 to 9% in 2007 (P < 0.05), whilst the proportion of EMRSA-15 rose commensurately, accounting for 85% of MRSA in 2007. Ciprofloxacin and erythromycin resistance were common amongst both EMRSA-15 and EMRSA-16. CONCLUSIONS EMRSA-15 and EMRSA-16 remain the main MRSA strains in bacteraemia in the UK, but the proportion of EMRSA-16 declined from the late 1990 s, thus preceding the general decline in MRSA bacteraemias that began in the middle of the present decade.

Emerging Trends in the Epidemiology of Invasive Group B Streptococcal Disease in England and Wales, 1991–2010

BACKGROUND Few cross-population studies examining the epidemiology of invasive group B streptococcal (GBS) disease have been undertaken. To identify longitudinal trends in the burden and characteristics of infections, national surveillance data on diagnoses in England and Wales from 1991 to 2010 were analyzed. METHODS A parallel review of laboratory-confirmed invasive GBS infection surveillance reports and isolates submitted to the national reference laboratory was undertaken. Cases were defined as GBS isolated from a normally sterile site. RESULTS A total of 21 386 reports of invasive GBS infection were made between 1991 and 2010. The annual rate of reports doubled over the 20 years from 1.48 to 2.99 per 100 000 population. Significant increases were seen in all age groups but most pronounced in adults. Rates of early-onset (0-6 days) infant disease fluctuated but showed a general rise between 2000 and 2010 from 0.28 to 0.41 per 1000 live births. Rates of late-onset (7-90 days) disease increased steadily between 1991 and 2010 from 0.11 to 0.29 per 1000 live births. Resistance to erythromycin increased markedly from 2.5% in 1991 to 15% in 2010. The distribution of serotypes varied according to patient age and over time with type III increasing among early-onset cases and decreasing in adults. CONCLUSIONS Although risk of invasive GBS infection remains highest within the first few days of life, the relative burden of disease is shifting toward adults. The rise in incidence and antibiotic resistance makes development of an effective and safe vaccine all the more pressing.

Increasing Pneumocystis Pneumonia, England, UK, 2000–2010

After an increase in the number of reported cases of Pneumocystis jirovecii pneumonia in England, we investigated data from 2000–2010 to verify the increase. We analyzed national databases for microbiological and clinical diagnoses of P. jirovecii pneumonia and associated deaths. We found that laboratory-confirmed cases in England had increased an average of 7% per year and that death certifications and hospital admissions also increased. Hospital admissions indicated increased P. jirovecii pneumonia diagnoses among patients not infected with HIV, particularly among those who had received a transplant or had a hematologic malignancy. A new risk was identified: preexisting lung disease. Infection rates among HIV-positive adults decreased. The results confirm that diagnoses of potentially preventable P. jirovecii pneumonia among persons outside the known risk group of persons with HIV infection have increased. This finding warrants further characterization of risk groups and a review of P. jirovecii pneumonia prevention strategies.

Incidence, Etiology, and Outcome of Bacterial Meningitis in Infants Aged <90 Days in the United Kingdom and Republic of Ireland: Prospective, Enhanced, National Population-Based Surveillance

BACKGROUND Bacterial meningitis remains a major cause of morbidity and mortality in young infants. Understanding the epidemiology and burden of disease is important. METHODS Prospective, enhanced, national population-based active surveillance was undertaken to determine the incidence, etiology, and outcome of bacterial meningitis in infants aged <90 days in the United Kingdom and Ireland. RESULTS During July 2010-July 2011, 364 cases were identified (annual incidence, 0.38/1000 live births; 95% confidence interval [CI], .35-.42). In England and Wales, the incidence of confirmed neonatal bacterial meningitis was 0.21 (n = 167; 95% CI, .18-.25). A total of 302 bacteria were isolated in 298 (82%) of the cases. The pathogens responsible varied by route of admission, gestation at birth, and age at infection. Group B Streptococcus (GBS) (150/302 [50%]; incidence, 0.16/1000 live births; 95% CI, .13-.18) and Escherichia coli (41/302 [14%]; incidence, 0.04/1000; 95% CI, .03-.06) were responsible for approximately two-thirds of identified bacteria. Pneumococcal (28/302 [9%]) and meningococcal (23/302 [8%]) meningitis were rare in the first month, whereas Listeria meningitis was seen only in the first month of life (11/302 [4%]). In hospitalized preterm infants, the etiology of both early- and late-onset meningitis was more varied. Overall case fatality was 8% (25/329) and was higher for pneumococcal meningitis (5/26 [19%]) than GBS meningitis (7/135 [5%]; P = .04) and for preterm (15/90 [17%]) compared with term (10/235 [4%]; P = .0002) infants. CONCLUSIONS The incidence of bacterial meningitis in young infants remains unchanged since the 1980s and is associated with significant case fatality. Prevention strategies and guidelines to improve the early management of cases should be prioritized.

The changing aetiology of paediatric bacteraemia in England and Wales, 1998-2007

Bacteraemia in children is a potentially life-threatening condition. The objective of this study was to determine trends in the aetiology of bacteraemia in children aged 1 month-15 years in England and Wales by collecting data voluntarily reported by National Health Service hospital microbiology laboratories. Over the 10-year period 1998-2007, a total of 51 788 bacteraemia cases involving 105 genera/species of bacteria were reported. Total annual reports of bacteraemia increased from 4125 to 6916, with a mean increase of 6.5 % per year (95 % CI: 1.3-12.1 %). In 2007, just over half the cases were accounted for by four groups of organisms: coagulase-negative staphylococci (28 %), Staphylococcus aureus (10 %), non-pyogenic streptococci (9 %) and Streptococcus pneumoniae (7 %). These organisms along with a further 13 species/genera accounted for 90 % of the cases. The commonest Gram-negative organisms were Neisseria meningitidis and Escherichia coli, which each accounted for 5 % of total bacteraemia reports in 2007. There was a significant decrease in reports of bacteraemia due to the three vaccine-preventable pathogens Haemophilus influenzae, N. meningitidis and Strep. pneumoniae, following the introduction of each vaccine programme or catch-up campaign. This study identified the commonest causes of bacteraemia in children in England and Wales, and highlighted the shifts in trends observed over time.

Exploring the Epidemiology of Hospital-Acquired Bloodstream Infections in Children in England (January 2009–March 2010) by Linkage of National Hospital Admissions and Microbiological Databases

BACKGROUND Hospital-acquired bloodstream infection (HA-BSI) requires immediate effective antibiotic treatment. However, there are no published national data for England that describe the pathogen profile and antibiotic resistance rates of HA-BSI in children. METHODS Probabilistic matching methods were used to link national data on microbiologically confirmed BSI to hospital in-patient admissions data for the period of January 2009-March 2010. HA-BSI was defined as a positive blood culture drawn from a child aged 1 month-18 years 2 or more days after admission (and before discharge). RESULTS A total of 8718 episodes of BSI was reported during the study period. Linkage allowed 82% of records to be matched, of which 23% (1734) were HA-BSI, giving a rate of 4.74 per 1000 admissions. The median age of infection was 1 year, and 54% of infections were in males. Methicillin resistance was seen in 83% and 17% of coagulase-negative staphylococci and Staphylococcus aureus, respectively. Penicillin resistance was rare in pyogenic streptococci but more common in viridans streptococci (39%). Among Gram-positive organisms, only 3% were vancomycin-resistant. The overall proportion of Gram-negative bacteria resistant to recommended empirical antibiotics (meropenem or piperacillin/tazobactam) was 5% and 16%, respectively, but <4% of isolates were resistant when either of these drugs were combined with gentamicin. CONCLUSIONS This study provides the first national estimates of the proportion of pediatric BSI that is hospital-acquired and describes the antimicrobial resistance of organisms causing infection. Pediatric HA-BSI remains unacceptably high; interventions must focus on identifying effective means of preventing HA-BSI, fostering antibiotic stewardship, and improving surveillance.

Empirical treatment of influenza-associated pneumonia in primary care: a descriptive study of the antimicrobial susceptibility of lower respiratory tract bacteria (England, Wales and Northern Ireland, January 2007–March 2010)

Objectives To determine the susceptibility of lower respiratory tract (LRT) isolates of Streptococcus pneumoniae, Staphylococcus aureus and Haemophilus influenzae to antimicrobial agents recommended by UK guidelines for treatment of pneumonia associated with influenza-like illness. Methods Analysis of antimicrobial susceptibility data from sentinel microbiology laboratories in England, Wales and Northern Ireland was carried out. Subjects comprised patients who had an LRT specimen taken in a general practitioner surgery or hospital outpatient setting between January 2007 and March 2010. The main outcome measurements were antimicrobial susceptibility trends of LRT isolates over time, between patient age groups and in different geographical regions. Results Susceptibility to tetracyclines or co-amoxiclav was high. Of the 70 288 and 45 288 isolates with susceptibility results for tetracyclines or co-amoxiclav, 96% and 92%, respectively, were susceptible. Overall susceptibility to ciprofloxacin, ampicillin/amoxicillin and macrolides was lower than for tetracyclines or co-amoxiclav and varied markedly by organism. There were few clinically relevant variations in susceptibility to doxycycline or co-amoxiclav over time, geographically or between age groups. Conclusions The data support the use of doxycycline or co-amoxiclav as appropriate empiric treatment for LRT infection caused by the pathogens investigated, for patients in primary care.

Reduction in erythromycin resistance in invasive pneumococci from young children in England and Wales

for gen. sp. 13BJ). The most noteworthy were the results for A. beijerinckii, A. junii and gen. sp. 13BJ. Whereas the former two species included both susceptible and resistant strains all eight strains of gen. sp. 13BJ yielded MICs 16 mg/L. It has recently been shown that therapy with colistin can be compromised by the selection and spread of colistin-resistant A. baumannii strains. Our data further indicate that resistance to colistin may be commonly present (A. junii, A. beijerinckii) in or even intrinsic (gen. sp. 13BJ) to some non-A. baumannii species. Although the colistin-resistant non-A. baumannii strains are rarely isolated from clinical specimens and these strains are usually susceptible to other antimicrobials (data on file), our findings emphasize the importance of precise species identification especially in reports on polymyxin resistance in Acinetobacter spp. Notably, resistance to colistin in A. baumannii has recently been associated with mutations in the PmrAB twocomponent system and it remains to be established whether this system also plays a role in the resistance of non-A. baumannii strains.

Vancomycin may not be necessary

The guidelines from the National Institute for Health and Clinical Excellence (NICE) on the empirical treatment of bacterial meningitis in children recommend intravenous ceftriaxone for children aged ≥3 months and cefotaxime plus ampicillin or amoxicillin for infants aged ≥3 months.1 2 The British National Formulary for Children ( BNF-C ) recommends similar empirical treatment with cefotaxime or cefotaxime and ampicillin, respectively.3 Whereas the BNF-C …