Alan P. Johnson

Bacteraemia and antibiotic resistance of its pathogens reported in England and Wales between 1990 and 1998: trend analysis

Abstract Objectives: Determination of causes, trends, and antibiotic resistance in reports of bacterial pathogens isolated from blood in England and Wales from 1990 to 1998. Design: Description of bacterial isolates from blood, judged to be clinically significant by microbiology staff, reported to the Communicable Disease Surveillance Centre. Setting: Microbiology laboratories in England and Wales. Subjects: Patients yielding clinically significant isolates from blood. Main outcome measures: Frequency and Poisson regression analyses for trend of reported causes of bacteraemia and proportions of antibiotic resistant isolates. Results: There was an upward trend in total numbers of reports of bacteraemia. The five most cited organisms accounted for over 60% of reports each year. There was a substantial increase in the proportion of reports of Staphylococcus aureus resistant to methicillin, Streptococcus pneumoniae resistance to penicillin and erythromycin, and Enterococcus faecalis and Enterococcus faecium resistance to vancomycin. No increase was seen in resistance of Escherichia coli to gentamicin. Conclusions: Reports from laboratories provide valuable information on trends and antibiotic resistance in bacteraemia and show a worrying increase in resistance to important antibiotics.

Editorial: Assessing the antimicrobial susceptibility of bacteria obtained from animals

The accurate performance of antimicrobial susceptibility testing of bacteria from animal sources and the correct presentation of the results is a complex matter. A review of the published literature revealed a number of recurring errors with regard to methodology, quality control, appropriate interpretive criteria, and calculation of MIC(50) and MIC(90) values. Although more subjective, there is also no consensus regarding the definition of multiresistance. This Editorial is intended to provide guidance to authors on how to avoid these frequently detected shortcomings.

Global spread of antibiotic resistance: the example of New Delhi metallo-β-lactamase (NDM)- mediated carbapenem resistance

The rapidity with which new types of antibiotic resistance can disseminate globally following their initial emergence or recognition is exemplified by the novel carbapenemase New Delhi metallo-β-lactamase (NDM). The first documented case of infection caused by bacteria producing NDM occurred in 2008, although retrospective analyses of stored cultures have identified the gene encoding this enzyme (blaNDM) in Enterobacteriaceae isolated in 2006. Since its first description, NDM carbapenemase has been reported from 40 countries worldwide, encompassing all continents except South America and Antarctica. The spread of NDM has a complex epidemiology involving the spread of a variety of species of NDM-positive bacteria and the inter-strain, inter-species and inter-genus transmission of diverse plasmids containing blaNDM, with the latter mechanism having played a more prominent role to date. The spread of NDM illustrates that antibiotic resistance is a public health problem that transcends national borders and will require international cooperation between health authorities if it is to be controlled.

Methicillin-resistant Staphylococcus aureus: the European landscape

Pan-European surveillance of bacteraemia caused by methicillin-resistant Staphylococcus aureus (MRSA) shows it to be a problem affecting all European countries, although there is marked geographical variation in prevalence. Although the proportion of S. aureus bacteraemia due to MRSA is declining in many countries, data from the European Antimicrobial Resistance Surveillance System (EARSS) for 2008 showed that in more than one-third of countries the proportion remained >25%. In contrast to bacteraemia, community-associated MRSA infection in Europe remains relatively uncommon. However, there appears to be an increasing problem involving transmission of MRSA (particularly sequence type 398) from colonized livestock, particularly pigs, to farm workers, abattoir workers and veterinarians who are in contact with such animals. Molecular analysis of isolates of MRSA has shown that there has been spread of only a limited number of MRSA clones in Europe and that many of these clones show geographical clustering due to dissemination through regional healthcare networks. Despite our increasing understanding of the epidemiology of MRSA in Europe, MRSA infections continue to pose a significant public health challenge.

Assessing the antimicrobial susceptibility of bacteria obtained from animals

In recent years, antimicrobial resistance in bacteria of animal origin, including food-producing animals, pet and companion animals, fish and other aquatic animals as well as wild animals, has gained particular attention. Consequently, an increasing number of studies that include antimicrobial susceptibility testing have been published. However, an analysis of recently published articles revealed a number of frequently occurring shortcomings, which may have an impact either directly on the quality of the results obtained or on the conclusions drawn. This editorial is intended to highlight the major pitfalls and provide guidance for authors, and reviewers on the correct performance of antimicrobial susceptibility testing as well as the presentation of the obtained results and the proper comparison of data from different studies.

Trends in Fluoroquinolone (Ciprofloxacin) Resistance in Enterobacteriaceae from Bacteremias, England and Wales, 1990–1999

The Public Health Laboratory Service receives antibiotic susceptibility data for bacteria from bloodstream infections from most hospitals in England and Wales. These data were used to ascertain resistance trends to ciprofloxacin from 1990 through 1999 for the most prevalent gram-negative agents: Escherichia coli, Klebsiella spp., Enterobacter spp., and Proteus mirabilis. Significant increases in resistance were observed for all four species groups. For E. coli, ciprofloxacin resistance rose from 0.8% in 1990 to 3.7% in 1999 and became widely scattered among reporting hospitals. The prevalence of resistance in Klebsiella spp. rose from 3.5% in 1990, to 9.5% in 1996 and 7.1% in 1999, while that in Enterobacter spp. rose from 2.1% in 1990 to 10.5% in 1996 and 10.9% in 1999. For both Klebsiella and Enterobacter spp., most resistance was localized in a few centers. Resistance was infrequent and scattered in P. mirabilis, but reached a prevalence of 3.3% in 1999.

Trends among pathogens reported as causing bacteraemia in England, 2004–2008

The Health Protection Agency in England operates a voluntary surveillance system that collects data on bacteraemias reported by over 90% of laboratories in England. Trends in causative microorganisms reported between 2004 and 2008 were analyzed using a generalized linear model with a log link function for Poisson distribution. In 2008, 101,276 episodes of bacteraemia were reported; a rate of 189 per 100,000 population. More than one-half occurred in those aged over 65 years and males. The most common organisms reported were Escherichia coli (23%), coagulase-negative staphylococci (CNS) (16.9%) and Staphylococcus aureus (11.4%). Between 2004 and 2008, E. coli bacteraemia increased by 33% (p < 0.001); the species now accounts for more than 30% of bacteraemia in those aged over 75 years. There also were significant increases in bacteraemia caused by other Gram-negative pathogens and marked seasonal variation. Bacteraemia caused by S. aureus increased until 2005, with a decline after 2006 (p < 0.001) entirely due to methicillin-resistant strains. CNS bacteraemia have declined significantly since 2007. The renewed dominance of Gram-negative pathogens as major causes of bacteraemia in England is of particular concern because they are associated with a high morbidity and increasing resistance to antibiotics. Further investigation of the underlying causes and prevention strategies is a public health priority. Recent declines in methicillin-resistant S. aureus bacteraemia have not been reflected in other pathogens, including methicillin-susceptible S. aureus.

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.

Mandatory surveillance of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in England: the first 10 years

Since 2001 it has been mandatory for acute hospital Trusts (groups of hospitals under the same management) in England to report all cases of bacteraemia due to Staphylococcus aureus together with information on their susceptibility or resistance to methicillin. This allowed the incidence of methicillin-resistant S. aureus (MRSA) bacteraemia (expressed as the number of cases per 1000 occupied bed days) to be determined for each Trust. In late 2005, the scheme was enhanced to collect demographic, clinical and epidemiological information on each case using a web-based data collection system. Analysis of this mandatory dataset has provided important information on the trends in MRSA bacteraemia in England and has documented a year-on-year decrease in incidence since 2006, following a government initiative in which Trusts were tasked with halving their MRSA bacteraemia rates over a 3 year period. In addition, the enhanced mandatory surveillance scheme has captured a wealth of data that have helped to further define the epidemiology of MRSA bacteraemia. It is to be hoped that based on the English experience of mandatory surveillance, other countries will consider the implementation of similar schemes, not only for MRSA but for other pathogens of public health importance.

Characterization of Group B Streptococci Recovered from Infants with Invasive Disease in England and Wales

Group B streptococci (GBS) are a major cause of invasive disease in infants, with enhanced surveillance in England and Wales showing an incidence of 0.74 cases per 1000 live births and a mortality rate of 8%. Among 353 isolates obtained during enhanced surveillance, the predominant serotypes were III (48%), Ia (27%), and V (10%), and the remainder comprised Ib, II, IV, VI, and VII; 3% were not typable. Isolates from patients with early-onset disease had serotypes III (38%), Ia (32%), and V (13%), with late-onset disease having a higher incidence of type III (67%) strains. Patients infected with serotype III strains had a higher rate of meningitis, and those with type V strains had a higher mortality rate. Isolates were susceptible to penicillin and ampicillin, but 4% were resistant to erythromycin, and 91% were resistant to tetracycline. A trivalent vaccine containing capsular polysaccharides III, Ia, and V could theoretically provide coverage against 85% of the cases of GBS disease among infants in England and Wales.