Effectiveness of an antifungal stewardship programme at a London teaching hospital 2010-16.

Background: The need for antifungal stewardship is gaining recognition with increasing incidence of invasive fungal infection (IFI) and antifungal resistance alongside the high cost of antifungal drugs. Following an audit showing suboptimal practice we initiated an antifungal stewardship programme and prospectively evaluated its impact on clinical and financial outcomes. Patients and methods: From October 2010 to September 2016, adult inpatients receiving amphotericin B, echinocandins, intravenous fluconazole, flucytosine or voriconazole were reviewed weekly by an infectious diseases consultant and antimicrobial pharmacist. Demographics, diagnosis by European Organization for Research and Treatment of Cancer (EORTC) criteria, drug, indication, advice, acceptance and in-hospital mortality were recorded. Antifungal consumption and expenditure, and candidaemia species and susceptibility data were extracted from pharmacy and microbiology databases. Results: A total of 432 patients were reviewed, most commonly receiving AmBisome® (35%) or intravenous fluconazole (29%). Empirical treatment was often unnecessary, with 82% having no evidence of IFI. Advice was given in 64% of reviews (most commonly de-escalating or stopping treatment) and was followed in 84%. Annual antifungal expenditure initially reduced by 30% (£0.98 million to £0.73 million), then increased to 20% above baseline over a 5 year period; this was a significantly lower rise compared with national figures, which showed a doubling of expenditure over the same period. Inpatient mortality, Candida species distribution and rates of resistance were not adversely affected by the intervention. Conclusions: Provision of specialist input to optimize antifungal prescribing resulted in significant cost savings without compromising on microbiological or clinical outcomes. Our model is readily implementable by hospitals with high numbers of at-risk patients and antifungal expenditure.

Shift in dominant hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) clones over time.

OBJECTIVES: The majority of HA-MRSA infections are caused by endogenous infection and by only a small number of clones. The reasons for the success of some clones over others are unknown. METHODS: We investigated the evolution of an MRSA population from a large, acute-care teaching hospital in London, UK over a 10 year period. MRSA incidence and antibiotic prescribing were correlated with changes in resistance genes and prevalence of clonal groups. RESULTS: Three clones caused the majority of infections, CC30 SCCmecII (EMRSA-16), CC22 SCCmecIV (EMRSA-15) and ST239 SCCmecIII. Clones that were multidrug resistant were selected for, and CC22 became dominant once it acquired a wide range of extra resistance genes. CC22 MRSA was also the fittest clone in an independent growth assay and a competition assay, and had a greater ability to survive desiccation. No individual isolate was fully drug resistant, and there was evidence of substantial horizontal gene transfer (HGT) as well as resistance gene loss within the clonal groups. The exception was fluoroquinolone resistance, which was rarely lost by any of the dominant hospital clones, suggesting that this resistance contributes to selection and survival of HA-MRSA. In support of this, a decrease in hospital-wide ciprofloxacin (a fluoroquinolone) prescribing was strongly associated with an overall decrease in MRSA infection. CONCLUSION: Our data suggest successful HA-MRSA clones such as CC22 SCCmecIV are resistant to fluoroquinolones as well as fitter and able to acquire, but not necessarily accumulate, resistance to a wide range of additional antibiotics.

Are nasal carriers of Staphylococcus aureus more likely to become colonized or infected with methicillin-resistant Staphylococcus aureus on admission to a hospital?

Of 840 patients at hospital admission, 2.7% were positive for methicillin-resistant Staphylococcus aureus (MRSA) and 22.3% were positive for methicillin-susceptible S. aureus (MSSA). During the next 8 months, 4.8% of the MSSA-positive patients acquired MRSA with no lineage association. A total of 5.2% of noncarriers acquired MRSA. We find no evidence that colonized hosts are more susceptible to acquiring MRSA.

DNA microarrays for virus detection in cases of central nervous system infection.

A low-density, high-resolution diagnostic DNA microarray comprising 38 gene targets for 13 viral causes of meningitis and encephalitis was constructed. The array has been used for the detection of multiplex PCR-amplified viruses in cerebrospinal fluid (CSF) and non-CSF specimens. A total of 41 clinical specimens were positive for echoviruses (23 samples), herpes simplex virus type 2 (4 samples), varicella-zoster virus (4 samples), human herpesvirus 7 (1 sample), human herpesvirus 6A (1 sample) and 6B (2 samples), Epstein-Barr virus (three samples), polyomavirus JC (1 sample), and cytomegalovirus (2 samples). Probes for herpes simplex virus type 1, polyomavirus BK, and mumps and measles viruses were also included on the array. Three samples were false negative by the microarray assay due to discordant results between the multiplex PCR for all 13 viruses simultaneously and the virus-specific PCR alone. Fifteen CSF specimens were true negative. The clinical sensitivity, specificity, and negative and positive predictive values of the assay were 93, 100, 100, and 83%, respectively, when the results were compared to those of the single-virus PCR, which was used as the "gold standard." The microarray-based virus detection assay is qualitative and provides a single-format diagnostic tool for the detection of panviral CNS infections.

Evolutionary relationships among strains of Mycobacterium tuberculosis with few copies of IS6110.

Molecular typing of Mycobacterium tuberculosis by using IS6110 shows low discrimination when there are fewer than five copies of the insertion sequence. Using a collection of such isolates from a study of the epidemiology of tuberculosis in London, we have shown a substantial degree of congruence between IS6110 patterns and both spoligotype and PGRS type. This indicates that the IS6110 types mainly represent distinct families of strains rather than arising through the convergent insertion of IS6110 into favored positions. This is supported by identification of the genomic sites of the insertion of IS6110 in these strains. The combined data enable identification of the putative evolutionary relationships of these strains, comprising three lineages broadly associated with patients born in South Asia (India and Pakistan), Africa, and Europe, respectively. These lineages appear to be quite distinct from M. tuberculosis isolates with multiple copies of IS6110.