Regional variation in ampicillin and trimethoprim resistance in Escherichia coli in England from 1990 to 1997, in relation to antibacterial prescribing.

Over 200 hospitals in England report resistance data for bacteraemia and meningitis isolates to the Public Health Laboratory Service. We reviewed ampicillin and trimethoprim resistance rates from 1990 to 1997 for Escherichia coli, which is the species reported most frequently from these bacteraemias. Ampicillin resistance was relatively stable over time, but varied between Health Regions. The proportion of ampicillin-resistant E. coli in the East Anglia region remained

Are routine sensitivity test data suitable for the surveillance of resistance? Resistance rates amongst Escherichia coli from blood and CSF from 1991-1997, as assessed by routine and centralized testing.

Surveillance of antibiotic resistance can be undertaken by compilation of routine data or by central testing of isolates. Routine results can be obtained cheaply and in sufficient quantities for correlation with population and prescribing denominators but there is concern about their quality. As one of a series of ongoing studies to assess this quality, we compared the proportions of resistance amongst Escherichia coli from patients with bacteraemia or meningitis between 1991 and 1997 (i) as recorded in routine data reported to the PHLS and (ii) as found in tests performed at the PHLS Laboratory of Enteric Pathogens (LEP). These two data sets both showed an overall upward trend in the proportion of isolates resistant to ampicillin, trimethoprim, gentamicin and ciprofloxacin. The average annual percentage increase in resistance was estimated in separate logistic regression models, and 95% confidence intervals (CI) were determined. The annual percentage increases in the proportions of isolates reported resistant were similar in the two data sets for trimethoprim, gentamicin and ciprofloxacin but differed for ampicillin. The upward trends were statistically significant except for gentamicin resistance in the LEP data set, where the 95% CI straddled zero. The proportions of resistant isolates for each antibiotic in the two data sets each year were in poorer agreement than the trends; however, the 95% CI of the difference of proportions resistant between the routine and LEP data sets straddled zero in 4 or 5 of the 7 years studied. Some discrepancies might be explained by geographical bias in the sampling or by differences in definitions of resistance. Thus (i) the proportion of resistant isolates tested at LEP almost always fell within the ranges bounded by the highest and lowest proportions for individual Regional Health Authorities, as recorded in the routine data, and (ii) the fact that LEP consistently recorded less gentamicin resistance but more ciprofloxacin resistance than the routine could be explained by breakpoint differences. We conclude that routine susceptibility data for ampicillin, ciprofloxacin, gentamicin and trimethoprim appear sound for E. coli and might be suitable for correlation with other data, e.g. for prescribing.

In-vitro activity of sanfetrinem against isolates of Streptococcus pneumoniae and Staphylococcus aureus.

The activity of sanfetrinem (previously GV104326), was assessed against 168 isolates of Streptococcus pneumoniae and 90 isolates of Staphylococcus aureus. These isolates included a range of serotypes or phage types, and varied in their susceptibility to other antibiotics. Sanfetrinem exhibited good anti-pneumococcal activity, with MIC90s of < or = 0.007 mg/L and 0.5 mg/L for penicillin-susceptible and penicillin-resistant isolates, respectively. Sanfetrinem was also active against methicillin-susceptible staphylococci (MIC90 = 0.06 mg/L). However, the MICs of sanfetrinem for isolates with methicillin MICs of 8-16 mg/L and > or = 32 mg/L were 0.25-1 mg/L and 8->32 mg/L, respectively.

Serogroups/types and antibiotic resistance of referred isolates of Streptococcus pneumoniae: 1993 to 1995.

Surveillance of prevalent serogroups/types of Streptococcus pneumoniae and their susceptibility to antimicrobial agents is important for understanding the epidemiology of pneumococcal infections and for guiding empirical treatment. Current vaccines for prevention of pneumococcal infection utilise serotype specific antigens, so knowledge of the prevalence of particular serotypes is relevant to vaccine use and development. Five thousand seven hundred and ninety-six isolates of S. pneumoniae from separate patients were serogrouped or serotyped by the Streptococcus and Diphtheria Reference Unit between 1993 and 1995. Antibiotic susceptibility testing was carried out by the Antibiotic Reference Unit on 3821 (65.9%) of these isolates. A total of 40 distinct serogroups/types, together with a small number of non-typable isolates, were noted over the three year period. The same five serogroups/types (6, 9, 14, 19, and 23) occurred most commonly in each year of the study, not only in the total population of isolates studied, but also in isolates obtained from blood or cerebrospinal fluid, and among isolates with antibiotic resistance. Ninety-six per cent of the isolates belonged to serogroups/types included in the currently available 23-valent capsular polysaccharide pneumococcal vaccine; the conjugate petna-, hepta-, and nonavalent vaccines covered 51%, 75%, and 80% of isolates respectively. The nonavalent vaccine offers the most promise as 74% of all blood and cerebrospinal fluid isolates and 90% of antibiotic resistant isolates belonged to serogroups or types included in this formulation.

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.

Prevalence of antibiotic resistance and serotypes in pneumococci in England and Wales: results of observational surveys in 1990 and 1995.

OBJECTIVE: To assess the prevalence of antibiotic resistance and serotype distribution among pneumococci in England and Wales in 1990 and 1995. DESIGN: Observational surveys in March 1990 and March 1995. During two weeks in each survey period all pneumococci isolated in public health laboratories in England and Wales were collected and assessed for sensitivity to antibiotics and the distribution of serogroups or serotypes. SETTING: The network of public health laboratories throughout England and Wales. SUBJECTS: 1127 individual patient isolates of Streptococcus pneumoniae obtained during the two surveys. MAIN OUTCOME MEASURES: Sensitivity or resistance to a range of antibiotics; serogroup or serotype. RESULTS: The prevalence of intermediate or full resistance to penicillin increased from 1.5% in 1990 to 3.9% in 1995 and resistance to erythromycin increased from 2.8% to 8.6%. About 92% of isolates belonged to serogroups or serotypes included in the currently available pneumococcal vaccine. CONCLUSION: Resistance to penicillin and erythromycin has increased among pneumococci in England and Wales. Continued surveillance to assess further increases in the prevalence of pneumococcal resistance to antibiotics is essential.

Fungal infections: a survey of laboratory services for diagnosis and treatment.

A questionnaire on the services provided and the methods used for the diagnosis of fungal infections and for the support of antifungal chemotherapy was sent to members of the British Society for Medical Mycology (BSMM) and the British Society for Antimicrobial Chemotherapy (BSAC). Ninety-five responses from general microbiology laboratories in the United Kingdom were analysed, and we compared services provided by laboratories that serve a transplant unit with those offered by other laboratories. We estimate that about 150 cases of cryptococcosis, 500 to 600 of candidaemia, and 300 to 400 of invasive aspergillosis are identified by laboratories in the United Kingdom (UK) each year. The clinical laboratories are aware of the importance of fungal infection, but rely heavily on reference services. In some laboratories, however, the degree of investigation of specimens and the procedures in use are inadequate for diagnosing systemic mycoses and determining the susceptibility of isolates to antifungal agents. The balance between reference and local services requires attention and external quality assurance needs to be applied effectively. In addition, effective methods for the diagnosis of systemic mycoses, and reliable and practicable methods for determining the susceptibility of isolates to antifungal agents, are needed urgently.

Detection of the mec-A gene and phenotypic detection of resistance in Staphylococcus aureus isolates with borderline or low-level methicillinresistance.

Eighty-three isolates of Staphylococcus aureus for which MICs of methicillin of 4-16 mg/L had previously been recorded were tested for the presence of the mecA gene with a DNA probe and a PCR assay. There was complete agreement between the results obtained by these methods; 39 isolates were mecA-positive and 44 were mecA-negative. Using the presence of mecA as the defining standard, several phenotypic methods for determining resistance to methicillin were evaluated and a high-inoculum, agar-incorporation breakpoint test was found to offer the best combination of high sensitivity and high specificity. However twenty-seven of the 44 mecA-negative strains were methicillin-resistant according to agar dilution MICs (MIC > 4 mg/L on at least one of the four media used) but none had MICs exceeding 32 mg/L. One of the mecA-positive strains had a methicillin MIC of only 8 mg/L and did not appear to be heteroresistant. The clinical significance of these two groups of 'atypical' isolates may need further investigation. This study highlights the problems of detecting reliably S. aureus with low level methicillin resistance by phenotype methods and the usefulness of direct detection of the mecA gene.

Antifungal drug susceptibility testing. Working Party of the British Society for Antimicrobial chemotherapy.

This article describes the current situation with regard to intrinsic and acquired resistance to antifungal compounds and progress with the development of standardized methods of susceptibility testing for amphotericin B, flucytosine, and the azoles. Recommendations for testing of isolates from patients destined to receive antifungal drug treatment, or in whom therapeutic failure or relapse is suspected, are presented.

Current perspectives on glycopeptide resistance.

In the last 5 years, clinical isolates of gram-positive bacteria with intrinsic or acquired resistance to glycopeptide antibiotics have been encountered increasingly. In many of these isolates, resistance arises from an alteration of the antibiotic target site, with the terminal D-alanyl-D-alanine moiety of peptidoglycan precursors being replaced by groups that do not bind glycopeptides. Although the criteria for defining resistance have been revised frequently, the reliable detection of low-level glycopeptide resistance remains problematic and is influenced by the method chosen. Glycopeptide-resistant enterococci have emerged as a particular problem in hospitals, where in addition to sporadic cases, clusters of infections with evidence of interpatient spread have occurred. Studies using molecular typing methods have implicated colonization of patients, staff carriage, and environmental contamination in the dissemination of these bacteria. Choice of antimicrobial therapy for infections caused by glycopeptide-resistant bacteria may be complicated by resistance to other antibiotics. Severe therapeutic difficulties are being encountered among patients infected with enterococci, with some infections being untreatable with currently available antibiotics.

An audit of ciprofloxacin use in a district general hospital.

An audit of ciprofloxacin use at Southmead Hospital, Bristol was carried out for forty patients treated in early 1992 employing a modified Delphi technique with six assessors. Most patients assessed (20/40, 50%) had urinary tract infections (UTIs), 5/40 (12.5%) had chest infections, 4/40 (10%) had bacterial gastroenteritis and 3/40 (7.5%) had either bacteraemia or infection following an orthopaedic procedure. A likely bacterial pathogen was isolated from 32/40 (80%) of patients; 14/32 (44%) had Pseudomonas aeruginosa infections and from the remainder Enterobacteriaceae including Salmonella spp. (non-typhoid) were cultured. Oral therapy with ciprofloxacin was used in 37 (93%) of the 40 patients, and the three others received iv treatment. In 21/35 (60%) of patients where an assessment was made by majority scoring, a quinolone was felt to be clinically justified. A quinolone was least likely to be thought justified if the patient had a chest infection. The assessors had few concerns about the effectiveness or toxicity of ciprofloxacin but for 41% (14/34) of patients, where there was a majority opinion, a cheaper alternative was felt to be available; most of these patients had hospital-acquired UTIs caused by Enterobacteriaceae. The duration of therapy was felt to be too long in 35% (10/29) of patients, mainly because of prolonged treatment of UTIs. In some cases of P. aeruginosa infection the assessors would have used higher doses than those prescribed. Ciprofloxacin was the quinolone of choice in 24/32 (75%) of assessable cases. Norfloxacin was chosen to treat UTI due to multi-resistant Enterobacteriaceae in 6.2% (2/32) cases.(ABSTRACT TRUNCATED AT 250 WORDS)