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Alan P Johnson

Publications and source records attributed to Alan P Johnson.

At least 19 recordsLinked to original sources
PubMed2006

Trends in penicillin and macrolide resistance among pneumococci in the UK and the Republic of Ireland in relation to antibiotic sales to pharmacies and dispensing doctors.

It is widely believed that reducing antimicrobial usage should reduce resistance, although observational evidence is mixed. Pneumococci make ideal subjects to test this belief as they are widely surveyed and lack an animal reservoir. Accordingly, susceptibility data for pneumococci in the UK and Ireland were retrieved from the Health Protection Agency's LabBase/CoSurv system and from the European Antimicrobial Resistance Surveillance System (EARSS) and British Society for Antimicrobial Chemotherapy (BSAC) databases. The BSAC surveillance examines respiratory pneumococci; the other systems focus upon invasive organisms only, with the LabBase/CoSurv system being the most comprehensive, capturing data on most bacteraemias in England and Wales. National pharmacy sales data were obtained from the IMS Health MIDAS database and were modelled to the resistance data by logistic and linear regression analysis. All systems except for the BSAC respiratory surveillance data indicated that penicillin resistance has fallen significantly since 1999 in the UK, whereas macrolide resistance has been essentially stable, or has risen slightly. The data for Ireland were based on smaller sample sizes but suggested a fall in penicillin non-susceptibility from 1999 to 2004, with conflicting evidence for macrolide resistance. The recent decreasing trend in penicillin resistance is in contrast to a rising trend in England and Wales until (at least) 1997 and strongly rising macrolide resistance from 1989 to 1993. UK pharmacy sales of macrolides and oral beta-lactams fell by ca. 30% in the late 1990s following increased concern about resistance, before stabilising or rising weakly; sales in Ireland were stable or rose slightly in the study period. We conclude that falling penicillin resistance in pneumococci followed reduced sales of oral beta-lactams to pharmacies in the UK, but a similar fall in macrolide sales was not associated with any fall in resistance. Stabilisation or decline in penicillin resistance has occurred in Ireland despite stable or increasing oral beta-lactam sales.

Anti-Bacterial Agents↗
PubMed2006

Back to the basics: epidemiology in the Journal of Antimicrobial Chemotherapy.

Good epidemiological methods and appropriate statistical analysis are cornerstones of any valid, reliable and publishable epidemiological study. This editorial summarizes epidemiological studies published in the Journal of Antimicrobial Chemotherapy (12 issues, May 2005--April 2006) with respect to study objective, type and design. A significant proportion of these studies started off with a single study group. Drawing on this finding, various methodological aspects of choosing a sampling frame and of sampling methods are reviewed.

Epidemiologic Studies↗
PubMed2006

Prevalence and mechanisms of cephalosporin resistance in Enterobacteriaceae in London and South-East England.

OBJECTIVES: To investigate the molecular epidemiology of Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLs) in London and South-East England. METHODS: A prospective study involving 16 hospital microbiology laboratories in London and South-East England was undertaken over a 12 week period. Each laboratory submitted up to 100 consecutive cephalosporin-resistant Enterobacteriaceae isolates judged clinically significant by microbiology staff. Centralized testing was undertaken to confirm organism identification and cephalosporin resistance and to analyse resistance mechanisms. RESULTS: The predominant mechanism of cephalosporin resistance in isolates from both hospital and community settings was the production of CTX-M-type ESBLs, with CTX-M-producing Escherichia coli as the most numerous resistant organism overall. Other major mechanisms of cephalosporin resistance included production of non-CTX-M ESBLs and AmpC beta-lactamases. Most ESBL (both CTX-M and non-CTX-M) producers were multiply resistant to non-beta-lactam antibiotics, including trimethoprim, ciprofloxacin and gentamicin. CONCLUSIONS: CTX-M enzymes, which were unrecorded in the UK prior to 2000, have become the major mechanism of cephalosporin resistance in Enterobacteriaceae in South-East England. E. coli has overtaken Klebsiella and Enterobacter spp. to become the major host for ESBLs. Due to the multiple antibiotic resistance exhibited by many ESBL-producers, these changes have major implications for antimicrobial therapy.

Adolescent↗
PubMed2005

Surveillance and epidemiology of MRSA bacteraemia in the UK.

Surveillance of bacteraemia caused by methicillin-resistant Staphylococcus aureus (MRSA) in the UK has involved collection of data from hospital microbiology laboratories via several mechanisms, including a voluntary reporting scheme that has been operational in England and Wales since 1989 and mandatory reporting schemes that have been running independently in England, Wales, Scotland and Northern Ireland since 2001. In addition, surveillance schemes involving panels of participating sentinel laboratories that submit isolates for centralized susceptibility testing, such as the Bacteraemia Resistance Surveillance Programme run by the BSAC, have also been established. Each of these data sources have particular advantages, but they also have their individual limitations, with the result that they each give an incomplete picture if considered in isolation. However, by pooling the findings from these different but complementary surveillance programmes, a much more comprehensive and credible picture of the problem posed by MRSA is produced. These schemes have shown both a dramatic rise in the total numbers of cases of S. aureus bacteraemia reported annually and an increase in the proportion of such cases that involve MRSA (from 2% in 1990 to >40% in the early 2000s), although the most recent data indicate a slight reversal of these trends. Characterization of isolates of MRSA shows a marked temporal relationship between the rise in MRSA bacteraemias and the emergence and spread of two strains of epidemic MRSA, EMRSA-15 and EMRSA-16. Surveillance and control of MRSA infection continue to be high profile and further developments to the mandatory surveillance system in England are likely in the near future.

Bacteremia↗
PubMed2005

Susceptibility to moxifloxacin of pneumococci isolated in English hospitals participating in the European Antimicrobial Resistance Surveillance System (EARSS) in 2003.

Susceptibility to moxifloxacin, penicillin and erythromycin was determined for 592 invasive Streptococcus pneumoniae collected from 20 English hospitals participating in the European Antimicrobial Resistance Surveillance System (EARSS) during 2003. Resistance to moxifloxacin, penicillin and erythromycin was observed in 0.8%, 5.4% and 13% of the isolates, respectively. These results show that the large majority of pneumococci were susceptible to moxifloxacin in 2003, the year when it was licensed for clinical use in the UK.

Anti-Bacterial Agents↗
PubMed2004

Activity of dalbavancin against staphylococci and streptococci, assessed by BSAC and NCCLS agar dilution methods.

BACKGROUND: Dalbavancin is a long-half-life (9-12 days) glycopeptide, now in Phase 3 development. Its pharmacokinetics may facilitate home intravenous therapy, early discharge and long prophylaxis. METHODS: Dalbavancin and comparators were tested in vitro against staphylococci and streptococci to determine (i) activity and (ii) the comparability of agar dilution MICs by the BSAC and the NCCLS methods. The test panels comprised 92-93 isolates each of Staphylococcus aureus, coagulase-negative staphylococci (CoNS) and 'viridans' streptococci, chosen for epidemiological diversity and to over-represent strains resistant to conventional agents, including teicoplanin. RESULTS: Dalbavancin MICs by the BSAC and NCCLS methods generally were identical, or else those by the BSAC method were two-fold lower. In both cases the MIC distributions of dalbavancin within species groups were unimodal, with peaks at 0.25, 0.12/0.25 and 0.12 mg/L for S. aureus, CoNS and viridans streptococci, respectively. MIC differences between the BSAC and NCCLS methods were similarly small for other glycopeptides and, generally, non-glycopeptides. Dalbavancin MICs were mostly two- to 16-fold below those of vancomycin and dalbavancin-like vancomycin-remained highly active against teicoplanin-non-susceptible staphylococci. CONCLUSIONS: Dalbavancin has good activity versus streptococci and staphylococci, including teicoplanin-resistant strains. MICs by BSAC and NCCLS agar dilution methods were comparable to each other; slightly lower MIC values, nevertheless, have been recorded by broth microdilution.

Anti-Bacterial Agents↗
PubMed2004

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.

Anti-Bacterial Agents↗
PubMed2004

Calcium-supplemented daptomycin Etest strips for susceptibility testing on Iso-Sensitest agar.

OBJECTIVE: Iso-Sensitest agar (ISA), which is recommended by the BSAC for routine susceptibility testing of staphylococci and enterococci, contains insufficient calcium for testing daptomycin. Isotonic agar supplemented with 50 mg/L calcium has been advocated, but is not routinely available in many laboratories. We evaluated a daptomycin Etest that incorporates a constant level of calcium throughout the daptomycin gradient, designed to give an appropriate concentration around the strip during testing, as an alternative for susceptibility testing on ISA. METHODS: Ninety-one isolates of Staphylococcus aureus (45 methicillin-susceptible, 46 methicillin-resistant) and 90 enterococci (47 Enterococcus faecalis, 43 Enterococcus faecium) were tested. Daptomycin Etest MICs were determined on ISA, whereas agar dilution MICs were determined in parallel on Isotonic agar supplemented with calcium to 50 mg/L as a control. RESULTS: The agar dilution and Etest MIC ranges of daptomycin for S. aureus were 0.25-1 mg/L (mode 0.5 mg/L), and 0.125-2 mg/L (mode 0.25 mg/L), respectively. The corresponding MIC values for enterococci were 0.25-4 mg/L (mode, 1 mg/L) and 0.125-4 mg/L (mode, 2 mg/L). For staphylococci, 86% of the Etest MIC results were within one dilution of the agar dilution values, and for enterococci, 90% of the Etest MIC results met these criteria. When results from the two methods were not identical, there was a tendency for the Etest MIC values to be lower than the agar dilution values. CONCLUSIONS: This study shows that calcium-supplemented daptomycin Etests on ISA are an accurate and convenient alternative to calcium-supplemented Isotonic agar.

Anti-Bacterial Agents↗
PubMed2004

Low in vitro selection frequencies of enterococcal and staphylococcal mutants resistant to the oxazolidinone AZD2563.

Mutants with oxazolidinone MICs, 2- to 16-fold higher than those of parents, were selected from two of five clinical isolates of Enterococcus faecalis during exposure to AZD2563, but only at frequencies of ca. 10(-8). Resistance was not selected in Enterococcus faecium, Staphylococcus aureus or coagulase-negative staphylococci (CoNS). Mutants of one E. faecalis isolate had a G2576-->U 23S rRNA mutation; mutants derived from the second E. faecalis isolate lacked this mutation.

Enterococcus↗
PubMed2004

Antimicrobial resistance of invasive Streptococcus pneumoniae isolates in a British district general hospital: the international connection.

Between January 2000 and March 2001, Streptococcus pneumoniae were isolated from the blood of 56 patients admitted to a single district general hospital in the South-East of England. The serotype and antibiotic susceptibility were determined for all isolates and, for those resistant to erythromycin, the presence or absence of the mef(A) and erm(B) genes was determined by PCR. Multi-locus sequence typing, along with PFGE, was undertaken on all isolates resistant to penicillin or erythromycin and a group of antibiotic-susceptible isolates, to identify whether globally distributed pneumococcal clones, as described by the Pneumococcal Molecular Epidemiology Network (PMEN), were present in the study population. Three serotype 9V penicillin-resistant isolates were identified as belonging to the Spain9V-3 clone, while 14 erythromycin-resistant isolates of serotype 14 belonged to the England14-9 clone. A single multi-resistant isolate of serotype 6B, was found to be a single-locus variant of the Spain6B-2 clone. All 14 erythromycin-resistant serotype 14 isolates possessed the mef(A) gene, while the single multi-resistant isolate possessed the erm(B) gene. These findings confirm the wide distribution and clinical impact of PMEN clones, which accounted for all of the penicillin and erythromycin resistance observed amongst invasive isolates in a district general hospital over a 15-month period.

Anti-Bacterial Agents↗
PubMed2003

Ciprofloxacin resistance in Neisseria gonorrhoeae in England and Wales in 2002.

The Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) monitors trends in antimicrobial resistance in consecutive gonococcal isolates from 26 genitourinary medicine clinics in England and Wales. In 2002, 2204 gonococcal isolates were tested, and the overall prevalence of ciprofloxacin resistance (minimum inhibitory concentration > or =1 mg/L) was 9.8%, compared with 3.1% in 2001 and 2.1% in 2000. Between 2001 and 2002, prevalence of ciprofloxacin resistance increased two to three-fold, irrespective of recent sexual contact overseas, sex, or residence within or outside of London. These findings suggest that national and local treatment guidelines need to be reviewed urgently.

Anti-Infective Agents↗
PubMed2003

Antibiotic resistance in the intensive care unit setting.

Antibiotic resistance is an important factor influencing clinical outcome for patients in intensive care units. It is also associated with increased healthcare costs resulting from prolonged patient stays. The problem of antibiotic resistance is particularly acute in intensive care units because they house seriously ill patients who are predisposed to infection, as a result of which, antibiotic use is extremely common. Strategies for controlling resistance in intensive care units have focused on attempting to reduce unnecessary antibiotic use, while at the same time ensuring adequate antibiotic cover is provided. The formulation of policies for the effective use of antibiotics in individual intensive care units requires a multidisciplinary approach, entailing regular epidemiological surveillance, together with input from critical care specialists, infectious disease specialists and pharmacists.

Animals↗
PubMed2003

The future prospects of oxazolidinones.

The high rates of antimicrobial resistance seen among many Gram-positive pathogens means that there is an ongoing need for new antibacterial drugs. Currently, several pharmaceutical companies are investigating compounds belonging to a new class of anti-Gram-positive agents, the oxazolidinones, one member of which, linezolid, is licensed for clinical use. Interest in oxazolidinones is being stimulated by the results of recent trials demonstrating the excellent clinical efficacy of linezolid in a range of infections. Linezolid is also a relatively safe drug, the main toxicity issue relating to development of thrombocytopenia in some patients receiving prolonged courses. With regard to new oxazolidinones, there is particular interest in analogs that, in early laboratory evaluation, show enhanced activity against the respiratory pathogens Haemophilus influenzae and Moraxella catarrhalis. The future potential of the oxazolidinones will depend on the antibacterial spectra, pharmacokinetic properties and toxicity profiles of new compounds, and the degree to which their clinical use may be affected by the emergence of oxazolidinone-resistant pathogens.

Animals↗
PubMed2002

In vitro activity of a novel oxazolidinone, AZD2563, against randomly selected and multiresistant Gram-positive cocci.

The in vitro activity of AZD2563, a novel oxazolidinone, was assessed against 595 Gram-positive cocci, comprising recent surveillance isolates and a collection of resistant (including multiresistant), epidemiologically diverse isolates. The MICs of AZD2563 for staphylococci, pneumococci and enterococci had narrow ranges, 0.25-2 mg/L, with modal MICs of 1 mg/L for staphylococci and pneumococci, and 1-2 mg/L for enterococci. AZD2563 was equally active against the surveillance isolates and those that had been selected for their multiresistance to other agents. The MICs of AZD2563 were either the same as those of linezolid or two-fold lower.

Acetamides↗
PubMed2002

A new UK strain of epidemic methicillin-resistant Staphylococcus aureus (EMRSA-17) resistant to multiple antibiotics.

An extensive outbreak in a hospital on the south coast of England in 2000, involving a multi-resistant strain of methicillin-resistant Staphylococcus aureus (MRSA) phenotypically similar to a strain periodically seen in several hospitals in that region since 1996, prompted a study to characterize the strain and determine the extent of its spread. Sixty-nine isolates with related phage patterns obtained between 1997 and 2000 from 19 hospitals were selected for study. Of these, 55 isolates had an identical PFGE profile (designated F1), and eight shared five other PFGE profiles (designated F2-F6), which differed from that of F1 by no more than three bands and were considered related. Six isolates had PFGE profiles that differed from F1-F6 by 9-18 bands and were considered to be distinct strains. The 63 isolates of profiles F1-F6 were considered to comprise a single strain and were phenotypically identical, being urease positive and resistant to multiple antibiotics including methicillin, ciprofloxacin, erythromycin, fusidic acid, rifampicin, gentamicin, kanamycin, neomycin, streptomycin and tetracycline, with or without high- or low-level mupirocin resistance. Borderline resistance to teicoplanin was also commonly noted. All but one of these 63 isolates contained the gene sea, with five also carrying the genes seg and sei, and two carrying tst. The isolates of this strain had been referred from 13 different hospitals, seven of which were on or near the south coast, four from London, one from the Midlands and one from the north of England. The isolates were thus considered to comprise an epidemic MRSA (EMRSA) strain, which has been designated EMRSA-17. The six non-EMRSA-17 isolates identified in the study were sensitive to fusidic acid and rifampicin, and came from six geographically diverse hospitals including three in Northern Ireland.

Cross Infection↗