Dorothy James

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.

Resistance to methicillin and other antibiotics in isolates of Staphylococcus aureus from blood and cerebrospinal fluid, England and Wales, 1989-95

BACKGROUND Methicillin-resistant Staphylococcus aureus (MRSA) strains are colonising hospital patients in most areas of England and Wales, UK. The extent to which they cause invasive infection can be gauged from their presence in isolates from blood or cerebrospinal fluid. METHODS About 200 clinical laboratories reported the results of susceptibility testing of between 4501 and 6370 isolates of S aureus from blood or cerebrospinal fluid in each of the years 1989-95. We assessed the rate of resistance to methicillin and other antibiotics for each of these years. FINDINGS Resistance to methicillin was stable at about 1.5% of isolates during 1989-91, but increased thereafter to 13.2% in 1995 (p < 0.001). At the same time there was a significant increase in the percentage of isolates resistant to erythromycin, clindamycin, ciprofloxacin, gentamicin, trimethoprim, and rifampicin (p < 0.001 for each)-resistance characteristics often seen in MRSA. Resistance to benzylpenicillin increased slightly but significantly (p < 0.001); resistance to fusidic acid was stable (p > 0.05); resistance to tetracycline decreased significantly (p < 0.001). INTERPRETATION Among cases of S aureus bacteraemia, the proportion due to MRSA has increased significantly. Bacteraemia due to MRSA has a poor prognosis, especially if not treated with suitable antibiotics. Therefore, these findings are important, especially for management of patients and the development of antibiotic policies.

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.

Susceptibility of Gram-positive bacteria from ICU patients in UK hospitals to antimicrobial agents.

Microbiologists in 25 sentinel laboratories were each asked to refer up to 100 clinically-significant Gram-positive bacteria isolated from consecutive intensive care unit (ICU) patients. A total of 1595 isolates were collected from patients in 23 hospitals; these included Staphylococcus aureus (47.6%), coagulase-negative staphylococci (CNS) (30.6%), enterococci (14.3%), pneumococci (2.8%) and other streptococci (3.5%). A few coryneforms, other bacilli and a Nocardia sp. were also collected. Rates of oxacillin resistance among S. aureus and CNS isolates were 59.3 and 78.5%, respectively. Vancomycin-resistant S. aureus were not detected, although two isolates (0.3%) were resistant to teicoplanin [minimum inhibitory concentrations (MICs) 8 mg/L]. In contrast, 13.7% of CNS were teicoplanin resistant (MICs 8-32 mg/L) and 1.2% were resistant to vancomycin. Among the enterococci, 72.5% were Enterococcus faecalis and 24.5% were Enterococcus faecium, the remainder including isolates of Enterococcus casseliflavus or Enterococcus gallinarum. Eighteen percent of E. faecium isolates were vancomycin-resistant, compared with only 3% of E. faecalis isolates. Rates of high-level gentamicin resistance in E. faecalis and E. faecium were 40 and 25%, respectively. Nine percent of pneumococci and streptococci were resistant to penicillin, with 7 and 11%, respectively, resistant to erythromycin. None of the isolates showed resistance to linezolid, with the MICs for the entire study population falling in the range of 0.5-4 mg/L.

Population structure and antibiotic resistance of Acinetobacter DNA group 2 and 13TU isolates from hospitals in the UK

A total of 287 Acinetobacter isolates belonging to DNA groups 2 (A. baumannii) and 13TU was collected consecutively from 46 hospitals and typed by randomly amplified polymorphic DNA fingerprinting with primers DAF-4 and ERIC-2. With a similarity coefficient of >/=72% as a cut-off value, 37 clusters of genotypically similar isolates (genotypes) were recognised. Four major clusters, found in 15, 12, 12 and 8 hospitals respectively, accounted for 42% of isolates, but only three of these predominant clusters were associated with outbreaks of infection in individual hospitals. Many of the isolates were resistant to multiple antibiotics, including expanded-spectrum beta-lactam agents, aminoglycosides, tetracyclines and fluoroquinolones, but >98% remained susceptible to carbapenems and colistin. Overall, the study demonstrated that a heterogeneous population of Acinetobacter DNA group 2 and 13TU isolates, frequently showing multiple resistance to antibiotics, was causing infections in UK hospitals, and that four predominant genotypes appeared to have disseminated among geographically distinct locations.

Fusidic-acid use and resistance

Sir—E M Brown and P Thomas (March 2, p 803) report locally high or rising rates of fusidic-acid resistance for Staphylococcus aureus in the UK, as do several correspondents on the British Medical Journal website. Particular concern is expressed about resistance in dermatology patients, in whom resistance rates of up to 34% are reported. Publication of national data is desirable to inform this discussion. Since 1989, the UK Public Health Laboratory Service has asked laboratories in England and Wales to report the antibiotic susceptibilities of isolates from bacteraemias. Reporting is voluntary, but more than 90% of laboratories contribute. The number of S aureus bacteraemias reported grew from 4800 in 1990, to higher than 12 000 in 2001, and the proportion of these attributable to meticillin-resistant S aureus (MRSA) rose from 1·3% to 43·6% (table). Dependent on the year, 55–75% of the reports for S aureus bacteraemia include susceptibility data for fusidic acid, suggesting that resistance has risen from 2% in 1990, to 6·8% in 2000 and 6·1% in 2001 (table), with rates currently being roughly equal among MRSA and meticillinsusceptible S aureus (MSSA). Higher fucidin resistance rates among MRSA in the early surveillance years have little importance, since MRSA were then infrequent in bacteraemias and belonged to other clones than the epidemic—(E)MRSA-15 and (E)MRSA-16 lineages that now predominate. These latter lineages are infrequently resistant to fusidic acid, but resistance is characteristic of some less common epidemic strains, such as (E)MRSA-17. Resistance may reflect heavy or increasing use of fusidic-acid preparations in retail and hospital pharmacies. From 1992 to 2001, according to IMS data, fusidic-acid sales have risen around 2·5-fold in the UK. Topical preparations in the community account for a growing proportion of total use (43·2% in 1992, 62·6% in 2001). There is also substantial use of oral preparations in hospitals and the community. Such heavy use—totalling more than 3 tonnes in 2001, nearly two-thirds of which was topical—is compatible with increasing resistance, especially among dermatological isolates. Resistant strains selected in dermatology patients may be later causes of more serious infections, including bacteraemias, in these patients or in others. In any event, it is disturbing that resistance should be increasing to a drug that, if used systemically and in combination, is beneficial even in the most severe staphylococcal infections.

Susceptibility testing challenges with ceftaroline, MRSA and a 1 mg/L breakpoint

OBJECTIVES A 1 mg/L susceptibility breakpoint for ceftaroline and staphylococci is universally agreed; EUCAST counts MIC >1 mg/L as resistant whereas CLSI and FDA count 2 mg/L as intermediate and >2 mg/L as resistant. We investigated whether routine diagnostic tests reliably distinguish MICs of 1 versus 2 mg/L. METHODS Thirty-five UK laboratories collected Staphylococcus aureus isolates and performed tests with 5 μg (as EUCAST) or 30 μg (as CLSI) discs and either confluent growth on Mueller-Hinton agar (as EUCAST and CLSI) or semi-confluent growth on Iso-Sensitest agar (as BSAC). They also ran Etests for MRSA. Reference MICs were determined centrally by CLSI and BSAC agar dilution. RESULTS We obtained paired local disc and central MIC results for 1607 S. aureus (33% MRSA). EUCASTs zone breakpoint recognized 56% of isolates found resistant in MIC tests, but the positive predictive value (PPV) for resistance was 11.0%; corresponding proportions by CLSI testing were 28.0% and 13.4%. The BSAC disc method detected 25% of resistant isolates, with a PPV of 18.2%. Essential agreement, ±1 dilution, of local Etests and central agar MICs was >95%, but only 20% of the isolates found non-susceptible by agar dilution were found non-susceptible by Etest and vice versa. Review for isolates with the modal MIC (0.25 mg/L) indicated that the same laboratories reported large or small zones irrespective of disc and method, implying systematic bias. CONCLUSIONS MRSA with ceftaroline MICs of 1 and 2 mg/L were poorly discriminated by routine methods. Solutions lie in greater standardization, automation or dosages justifying a higher breakpoint.