Restrictive antibiotic stewardship associated with reduced hospital mortality in gram-negative infection

Introduction: Antimicrobial stewardship has an important role in the control of Clostridium difficile infection (CDI) and antibiotic resistance. An important component of UK stewardship interventions is the restriction of broad-spectrum beta-lactam antibiotics and promotion of agents associated with a lower risk of CDI such as gentamicin. Whilst the introduction of restrictive antibiotic guidance has been associated with improvements in CDI and antimicrobial resistance evidence of the effect on outcome following severe infection is lacking. Methods: In 2008, Glasgow hospitals introduced a restrictive antibiotic guideline. A retrospective before/after study assessed outcome following gram-negative bacteraemia in the 2-year period around implementation. Results: Introduction of restrictive antibiotic guidelines was associated with a reduction in utilisation of ceftriaxone and co-amoxiclav and an increase in amoxicillin and gentamicin. 1593 episodes of bacteraemia were included in the study. The mortality over 1 year following gram-negative bacteraemia was lower in the period following guideline implementation (RR 0.852, P = 0.045). There was no evidence of a difference in secondary outcomes including ITU admission, length of stay, readmission, recurrence of bacteraemia and need for renal replacement therapy. There was a fall in CDI (RR 0.571, P = 0.014) and a reduction in bacterial resistance to ceftriaxone and co-amoxiclav but no evidence of an increase in gentamicin resistance after guideline implementation. Conclusion: Restrictive antibiotic guidelines were associated with a reduction in CDI and bacterial resistance but no evidence of adverse outcomes following gram-negative bacteraemia. There was a small reduction in one year mortality

Understanding non-vaccinating parents' views to inform and improve clinical encounters: A qualitative study in an Australian community

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Objectives To explain vaccination refusal in a sample of Australian parents. Design Qualitative design, purposive sampling in a defined population. Setting A geographically bounded community of approximately 30 000 people in regional Australia with high prevalence of vaccination refusal. Participants Semi structured interviews with 32 non-vaccinating parents: 9 fathers, 22 mothers and 1 pregnant woman. Purposive sampling of parents who had decided to discontinue or decline all vaccinations for their children. Recruitment via local advertising then snowballing. Results Thematic analysis focused on explaining decision-making pathways of parents who refuse vaccination. Common patterns in parents' accounts included: perceived deterioration in health in Western societies; a personal experience introducing doubt about vaccine safety; concerns regarding consent; varied encounters with health professionals (dismissive, hindering and helpful); a quest for the real truth'; reactance to system inflexibilities and ongoing risk assessment. Conclusions We suggest responses tailored to the perspectives of non-vaccinating parents to assist professionals in understanding and maintaining empathic clinical relationships with this important patient group

Amino acid changes in the spike protein of feline coronavirus correlate with systemic spread of virus from the intestine and not with feline infectious peritonitis

Recent evidence suggests that a mutation in the spike protein gene of feline coronavirus (FCoV), which results in an amino acid change from methionine to leucine at position 1058, may be associated with feline infectious peritonitis (FIP). Tissue and faecal samples collected post mortem from cats diagnosed with or without FIP were subjected to RNA extraction and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) to detect FCoV RNA. In cats with FIP, 95% of tissue, and 81% of faecal samples were PCR-positive, as opposed to 22% of tissue, and 60% of faecal samples in cats without FIP. Relative FCoV copy numbers were significantly higher in the cats with FIP, both in tissues (P < 0.001) and faeces (P = 0.02). PCR-positive samples underwent pyrosequencing encompassing position 1058 of the FCoV spike protein. This identified a methionine codon at position 1058, consistent with the shedding of an enteric form of FCoV, in 77% of the faecal samples from cats with FIP, and in 100% of the samples from cats without FIP. In contrast, 91% of the tissue samples from cats with FIP and 89% from cats without FIP had a leucine codon at position 1058, consistent with a systemic form of FCoV. These results suggest that the methionine to leucine substitution at position 1058 in the FCoV spike protein is indicative of systemic spread of FCoV from the intestine, rather than a virus with the potential to cause FIP

Irish inquiry reports relating to perinatal deaths and pregnancy loss services

Aims: External inquiries are carried out following specific adverse events in healthcare, many in maternity care; to identify issues and make recommendations to improve standards of care. Methods: Ten publically-available national inquiry reports published between 2005-2018 relating to pregnancy loss services, were reviewed by 2 clinicians, separately, examining the content and recommendations from each report. Results: A total of 258 recommendations were made in 9 reports (90%). Five inquiries (50%) clearly stated that affected families were involved and four (40%) involved affected clinical staff. In 9 reports (90%) recommendations included: increase workforce staffing and/or training, strengthen clinical governance, enhance adverse incident management and comprehensive data collection e.g. maternity outcomes. Only two inquiry reports (20%) stated that feedback was sought from key stakeholders prior to publication. Conclusion: A collaborative and standardised inquiry process involving and supporting all persons affected as well as key stakeholders would ensure that all relevant issues are identified, recommendations are implemented and essential lessons are learned

Protective Immunity against Infection with <i>Mycoplasma haemofelis</i>

Hemoplasmas are potentially zoonotic mycoplasmal pathogens, which are not consistently cleared by antibiotic therapy. Mycoplasma haemofelis is the most pathogenic feline hemoplasma species. The aim of this study was to determine how cats previously infected with M. haemofelis that had recovered reacted when rechallenged with M. haemofelis and to characterize the immune response following de novo M. haemofelis infection and rechallenge. Five specific-pathogen-free (SPF)-derived naive cats (group A) and five cats that had recovered from M. haemofelis infection (group B) were inoculated subcutaneously with M. haemofelis. Blood M. haemofelis loads were measured by quantitative PCR (qPCR), antibody response to heat shock protein 70 (DnaK) by enzyme-linked immunosorbent assay (ELISA), blood lymphocyte cell subtypes by flow cytometry, and cytokine mRNA levels by quantitative reverse transcriptase PCR. Group A cats all became infected with high bacterial loads and seroconverted, while group B cats were protected from reinfection, thus providing the unique opportunity to study the immunological parameters associated with this protective immune response against M. haemofelis. First, a strong humoral response to DnaK was only observed in group A, demonstrating that an antibody response to DnaK is not important for protective immunity. Second, proinflammatory cytokine interleukin-6 (IL-6) mRNA levels appeared to increase rapidly postinoculation in group B, indicating a possible role in protective immunity. Third, an increase in IL-12p35 and -p40 mRNA and decrease in the Th2/Th1 ratio observed in group A suggest that a Th1-type response is important in primary infection. This is the first study to demonstrate protective immunity against M. haemofelis reinfection, and it provides important information for potential future hemoplasma vaccine design

An investigation of polymorphisms in innate and adaptive immune response genes in canine leishmaniosis

The outcome of infection with Leishmania infantum in dogs is variable, which is thought to be due to the nature of the immune response mounted by the host. As a consequence, the clinical signs and severity of canine leishmaniosis vary between individual dogs. Host immunogenetic factors might play an important role in determining the outcome of infection. The aim of this study was to examine polymorphisms in innate and adaptive immune response genes, to determine whether any of these were associated with susceptibility or resistance to L. infantum infection. Genomic DNA was obtained from two groups: pet dogs in endemic regions of Europe and a group of Beagles exposed to sand fly infection as part of a vaccine study. Genotyping was performed using a SNP (single nucleotide polymorphism) array for selected immune response genes. The first part of the study compared 62 clinical cases with 101 clinically unaffected dogs that were seronegative for Leishmania antibodies. One SNP in the CIITA gene demonstrated a significantly higher minor allele frequency in the case group, compared with the control group at the individual SNP level after permutation, but was not significant after correction for multiple testing. The second part of the study examined 48 Beagle dogs exposed to L. infantum over two transmission seasons. Twenty-seven dogs with a resistant phenotype (no evidence of clinical disease, seronegative at the end of the study period, negative on lymph node culture and only transiently PCR positive in bone marrow) were compared with 21 dogs demonstrating a susceptible phenotype (clinical disease, seropositive, positive lymph node culture and consistently PCR positive in bone marrow). Three SNPs in TLR3, two SNPs in PTPN22 and one SNP in TLR4 and IL1A were associated with the susceptible phenotype in the Beagle group at the individual SNP level after permutation analysis, but were not significant after correction for multiple testing. Further validation of these SNPs is required in a larger cohort of dogs, ideally with extreme phenotypes to confirm an association with the outcome of L. infantum infection

A novel variant in CMAH is associated with blood type AB in Ragdoll cats

Citation: Gandolfi, B., Grahn, R. A., Gustafson, N. A., Proverbio, D., Spada, E., Adhikari, B., . . . Helps, C. R. (2016). A novel variant in CMAH is associated with blood type AB in Ragdoll cats. Plos One, 11(5). doi:10.1371/journal.pone.0154973The enzyme cytidine monophospho-N-acetylneuraminic acid hydroxylase is associated with the production of sialic acids on cat red blood cells. The cat has one major blood group with three serotypes; the most common blood type A being dominant to type B. A third rare blood type is known as AB and has an unclear mode of inheritance. Cat blood type antigens are defined, with N-glycolylneuraminic acid being associated with type A and N-acetylneuraminic acid with type B. Blood type AB is serologically characterized by agglutination using typing reagents directed against both A and B epitopes. While a genetic characterization of blood type B has been achieved, the rare type AB serotype remains genetically uncharacterized. A genome-wide association study in Ragdoll cats (22 cases and 15 controls) detected a significant association between blood type AB and SNPs on cat chromosome B2, with the most highly associated SNP being at position 4,487,432 near the candidate gene cytidine monophospho-N-acetylneuraminic acid hydroxylase. A novel variant, c.364C>T, was identified that is highly associated with blood type AB in Ragdoll cats and, to a lesser degree, with type AB in random bred cats. The newly identified variant is probably linked with blood type AB in Ragdoll cats, and is associated with the expression of both antigens (N-glycolylneuraminic acid and N-acetylneuraminic acid) on the red blood cell membrane. Other variants, not identified by this work, are likely to be associated with blood type AB in other breeds of cat. © 2016 Gandolfi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Entre défiance et amitié... Des relations politiques, diplomatiques et militaires tourmentées entre le roi de France et le prince-évêque de Liège au bas Moyen Âge (XIIIe-XVe siècles)

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