Brendan Crowley

Detailed characterization of the first high-level azithromycin-resistant Neisseria gonorrhoeae cases in Ireland

Detailed characterization of the first high-level azithromycin-resistant Neisseria gonorrhoeae cases in Ireland

Emergence and Phylogenetic Analysis of Amantadine-Resistant Influenza A Subtype H3N2 Viruses in Dublin, Ireland, over Six Seasons from 2003/2004 to 2008/2009

Objectives: To determine the prevalence of amantadine-resistant influenza A viruses and perform genetic analysis of isolates collected in Dublin during six seasons (2003/2004 to 2008/2009). Methods: Known mutations in the matrix 2 gene (M2) conferring amantadine resistance were screened and phylogenetic analysis of the haemagglutinin gene (HA) performed. Results: Of 1,180 samples, 67 influenza A viruses were isolated, 88% of which were subtype H3N2. Amantadine resistance was only found in subtype H3N2 and increased dramatically from 7% in 2003/2004 to 90% in 2008/2009. A maximum likelihood tree of the HA gene of influenza A H3N2 isolates differentiated them into two distinct clades, clade N and clade S, where the majority of isolates were amantadine-resistant and amantadine-sensitive, respectively. The clades were distinguished by amino acid substitutions, S193F and D225N, which probably conferred a selective advantage for the spread of such viruses. Phylogenetic analysis showed some degree of antigenic drift when compared with the vaccine strain of the corresponding season. Conclusions: This study showed that circulation in Ireland of a distinct lineage, clade N, among H3N2 viruses favoured emergence of amantadine resistance. Furthermore, comparison of circulating Irish viruses and vaccine strains used in the northern hemisphere showed high similarity.

BK virus (BKV) plasma dynamics in patients with BKV‐associated hemorrhagic cystitis following allogeneic stem cell transplantation

The use of real‐time polymerase chain reaction testing in the investigation of BK virus (BKV)‐associated disease has been widely studied in renal transplant recipients; however, far less research has been done in this area with respect to the plasma BK viral load dynamics of BKV hemorrhagic cystitis (BKV‐HC) in hematopoietic stem cell transplant recipients.

Role of efflux in macrolide resistance in β-haemolytic streptococci of groups A, B, C and G collected in an Irish teaching hospital

There has been an increase in macrolide resistance in b-haemolytic streptococci (BHS) reported worldwide. Macrolide resistance rates among group A streptococci (GAS) are variable, and range from 2 to 32 % in areas of the USA and Canada, from 5 to 29 % within Europe, and are as high as 63 % in Taiwan (Leclercq, 2002). Furthermore, a recent study in Spain found erythromycin resistance to be 26.1 % in GAS, 15.7 % in group B streptococci (GBS), 5.3 % in group C streptococci (GCS) and 33.3 % in group G streptococci (GGS) (Merino Dı́az et al., 2008). Mechanisms that confer resistance to macrolide, lincosamide and streptogramin B (MLSB) antibiotics in BHS include target site modification by methylation of the 23S rRNA binding site. This mechanism is mediated by the erm gene, which confers cross-resistance to all MLSB antibiotics. Resistance can be either inducible (iMLSB), where the methylase is produced in the presence of an inducer (such as erythromycin), or constitutive (cMLSB), where the methylase is produced constitutively. Drug efflux, which has been increasingly recognized, is mediated by the mefA/E gene, which encodes a 12membered transmembrane protein that pumps out 14and 15-membered ring macrolides only, with the isolate remaining susceptible to 16-membered MLSB antibiotics (M phenotype). The third resistance mechanism occurs as a result of antibiotic inactivation. Resistance is usually conferred to only one of the three classes (M, L or S). In Enterococcus faecium the linB gene encodes lincosamide nucleotidyltransferase, which inactivates lincosamides, conferring resistance to clindamycin only (L phenotype). The latter phenotype has been reported in clinical isolates of GBS (Gygax et al., 2006). The only Irish data published on the prevalence of erythromycin resistance and mechanisms of resistance in BHS reviewed GBS only (Kiely et al., 2010). Surveillance data in an Irish tertiary-care centre showed an increase in macrolide resistance among BHS groups A, B, C and G recently. Erythromycin resistance increased from 10 % in 2004 to 14 % in 2009, while clindamycin resistance rates remained steady over the same period, 6 % in 2004 and 5 % in 2009. The aims of this study were to determine the prevalence of erythromycin resistance in BHS groups A, B, C and G from clinical isolates in the largest hospital in Ireland (St James’s Hospital). Furthermore, resistance mechanisms to macrolides were determined by molecular methods.

Fourteen Draft Genome Sequences for the First Reported Cases of Azithromycin-Resistant Neisseria gonorrhoeae in Ireland

ABSTRACT Here, we report the draft genome assemblies of 14 azithromycin-resistant Neisseria gonorrhoeae clinical isolates, representing the first such strains identified in Ireland. Among these isolates are the first reported highly resistant strains (MIC >256 mg/liter), which both belonged to the ST1580 sequence type.

T2Candida MR as a predictor of outcome in patients with suspected invasive candidiasis starting empirical antifungal treatment: a prospective pilot study

Objectives We assessed the potential role of T2Candida MR (T2MR) and serological biomarkers [β-d-glucan (BDG) or Candida albicans germ tube antibodies (CAGTA)], alone or in combination with standard cultures, for identifying patients with suspected invasive candidiasis (IC), who may benefit from maintaining antifungal therapy. Methods Prospective observational multicentre study including all adult patients receiving empirical antifungal therapy for suspected IC, from January to June 2017. CAGTA, BDG and T2MR were determined at baseline and at +2 and +4 days after enrolment. Primary endpoint was the diagnostic value of CAGTA, BDG and T2MR, alone or in combination with standard culture, to predict diagnosis of IC and/or mortality in the first 7 days after starting antifungal therapy (poor outcome). Results Overall, 14/49 patients (28.6%) had a poor outcome (7 died within the first 7 days of antifungal therapy, whereas 7 ended with a diagnosis of IC). CAGTA [3/14 (21.4%) versus 8/35 (22.9%), P = 1] and BDG [8/14 (57.1%) versus 17/35 (48.6%), P = 0.75] results were similar in poor- and good-outcome patients. Conversely, a positive T2MR was associated with a higher risk of poor outcome [5/14 (35.7%) versus 0/35 (0.0%) P = 0.0001]. Specificity and positive predictive value of a positive T2MR for predicting poor outcome were both 100%, with a negative predictive value of 79.6%. After testing the combinations of biomarkers/standard cultures and T2MR/standard cultures, the combination of T2MR/standard cultures showed a high capacity to discriminate patients with poor outcome from those with good clinical evolution. Conclusions T2MR may be of significant utility to identify patients who may benefit from maintaining antifungal therapy.