David R. Murdoch

Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data

Objectives To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect. Design Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials. Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015. Eligibility criteria for study selection Randomised, double blind, placebo controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome. Results 25 eligible randomised controlled trials (total 11u2009321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10u2009933 (96.6%) participants. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity <0.001). In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted odds ratio 0.81, 0.72 to 0.91) but not in those receiving one or more bolus doses (adjusted odds ratio 0.97, 0.86 to 1.10; P for interaction=0.05). Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L (adjusted odds ratio 0.30, 0.17 to 0.53) than in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (adjusted odds ratio 0.75, 0.60 to 0.95; P for interaction=0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted odds ratio 0.98, 0.80 to 1.20, P=0.83). The body of evidence contributing to these analyses was assessed as being of high quality. Conclusions Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit. Systematic review registration PROSPERO CRD42014013953.

Population‐based epidemiology of Staphylococcus aureus bloodstream infection in Canterbury, New Zealand

Background: Few contemporary reports describe population‐based incidence of Staphylcoccus aureus bloodstream infection (SABSI).

Pertussis-Associated Pneumonia in Infants and Children From Low- and Middle-Income Countries Participating in the PERCH Study

Background.u2003Few data exist describing pertussis epidemiology among infants and children in low- and middle-income countries to guide preventive strategies. Methods.u2003Children 1–59 months of age hospitalized with World Health Organization–defined severe or very severe pneumonia in 7 African and Asian countries and similarly aged community controls were enrolled in the Pneumonia Etiology Research for Child Health study. They underwent a standardized clinical evaluation and provided nasopharyngeal and oropharyngeal swabs and induced sputum (cases only) for Bordetella pertussis polymerase chain reaction. Risk factors and pertussis-associated clinical findings were identified. Results.u2003Bordetella pertussis was detected in 53 of 4200 (1.3%) cases and 11 of 5196 (0.2%) controls. In the age stratum 1–5 months, 40 (2.3% of 1721) cases were positive, all from African sites, as were 8 (0.5% of 1617) controls. Pertussis-positive African cases 1–5 months old, compared to controls, were more often human immunodeficiency virus (HIV) uninfected-exposed (adjusted odds ratio [aOR], 2.2), unvaccinated (aOR, 3.7), underweight (aOR, 6.3), and too young to be immunized (aOR, 16.1) (all P ≤ .05). Compared with pertussis-negative African cases in this age group, pertussis-positive cases were younger, more likely to vomit (aOR, 2.6), to cough ≥14 days (aOR, 6.3), to have leukocyte counts >20 000 cells/µL (aOR, 4.6), and to have lymphocyte counts >10 000 cells/µL (aOR, 7.2) (all P ≤ .05). The case fatality ratio of pertussis-infected pneumonia cases 1–5 months of age was 12.5% (95% confidence interval, 4.2%–26.8%; 5/40); pertussis was identified in 3.7% of 137 in-hospital deaths among African cases in this age group. Conclusions.u2003In the postneonatal period, pertussis causes a small fraction of hospitalized pneumonia cases and deaths; however, case fatality is substantial. The propensity to infect unvaccinated infants and those at risk for insufficient immunity (too young to be vaccinated, premature, HIV-infected/exposed) suggests that the role for maternal vaccination should be considered along with efforts to reduce exposure to risk factors and to optimize childhood pertussis vaccination coverage.

Legionnaires' disease caused by Legionella longbeachae: Clinical features and outcomes of 107 cases from an endemic area

Legionella longbeachae is a predominant cause of Legionnaires disease in some parts of the world, particularly in Australasia. Clinical reports of L.u2009longbeachae infection are limited to case reports or small case series, and culture‐confirmed cases.

Pneumococcal vaccine impact on otitis media microbiology: A New Zealand cohort study before and after the introduction of PHiD-CV10 vaccine.

UNLABELLEDnWe compared the microbiology of middle ear fluid (MEF) in two cohorts of children having ventilation tube (VT) insertion; the first in the era of 7-valent Streptococcus pneumoniae conjugate vaccine (PCV7) and the second following introduction of the ten-valent pneumococcal vaccine (PHiD-CV10).nnnMETHODSnDuring 2011 (Phase 1) and again in 2014 (Phase 2) MEF and NP samples from 325 children and 319 children were taken at the time of VT insertion. A matched comparison group had NP swabs collected with 137 children (Phase 1) and 154 (Phase 2). Culture was performed on all NP and MEF samples with further molecular identification of Haemophilus species, serotyping of S. pneumoniae, and polymerase chain reaction (PCR) testing on all MEF samples.nnnRESULTSnIn Phase 2 immunisation coverage with ⩾3 doses of PHiD-CV10 was 93%. The rate and ratios of culture and molecular detection of the 3 main otopathogens was unchanged between Phase 1 and Phase 2 in both MEF and NP. Haemophilus influenzae was cultured in one quarter and detected by PCR in 53% of MEF samples in both time periods. S. pneumoniae and Moraxella catarrhalis were cultured in up to 13% and detected by PCR in 27% and 40% respectively of MEF samples. H. influenzae was the most common organism isolated from NP samples (61%) in the children undergoing VT surgery whilst M. catarrhalis (49%) was the most common in the non-otitis prone group. 19A was the most prominent S. pneumoniae serotype in both MEF and NP samples in Phase 2. Of Haemophilus isolates, 95% were confirmed to be non-typeable H. influenzae (NTHi) over both time periods.nnnCONCLUSIONnFollowing implementation of PHiD-CV10 in New Zealand, there has been no significant change in the 3 major otopathogens in NP or MEF in children with established ear disease. For these children non-typeable H. influenzae remains the dominant otopathogen detected.

How recent advances in molecular tests could impact the diagnosis of pneumonia

ABSTRACT Molecular diagnostic tests have been the single major development in pneumonia diagnostics over recent years. Nucleic acid detection tests (NATs) have greatly improved the ability to detect respiratory viruses and bacterial pathogens that do not normally colonize the respiratory tract. In contrast, NATs do not yet have an established role for diagnosing pneumonia caused by bacteria that commonly colonize the nasopharynx due to difficulties discriminating between pathogens and coincidental carriage strains. New approaches are needed to distinguish infection from colonization, such as through use of quantitative methods and identification of discriminating cut-off levels. The recent realization that the lung microbiome exists has provided new insights into the pathogenesis of pneumonia involving the interaction between multiple microorganisms. New developments in molecular diagnostics must account for this new paradigm.

Comparison of the fast track diagnostics respiratory 21 and Seegene Allplex multiplex polymerase chain reaction assays for the detection of respiratory viruses

Abstract Background: Real-time multiplex PCR assays are increasingly used for respiratory virus detection, and offer automated analysis in a closed tube system, but they have the disadvantage of low-throughput due to multiplexing limitations. In this study, the established fast-track respiratory 21 assay (FTD) (fast-track diagnostics, Junglinster Luxembourg) was compared to the new Seegene Allplex assay (Seegene) (Seegene Inc. Seoul, Korea) which offers greater multiplexing as multiple targets can be detected in each fluorescence channel. The Seegene Allplex assay is quicker to perform than previous Seegene respiratory multiplex assays. Materials and methods: The assays were evaluated using 199 mostly upper respiratory tract samples. Results: A respiratory pathogen was found in 127/199 (63.8%) of samples by the FTD assay and 123/199 (61.8%) using the Seegene assay. Kappa agreement was between 0.87 and 1 for all targets except human bocavirus and adenovirus. Conclusion: Although the performance of the assays were similar, the Seegene assay had the advantage of simultaneous detection of two gene targets for each of the common Influenza A subtypes, improved throughput of 30 samples per run and automated result analysis. The FTD assay could only test 17 samples per run but validation for use on several different real-time thermal cyclers made it easier to integrate into an existing laboratory system. Both assays were cost effective compared to in-house multiplex PCR respiratory virus screening.

A One Health future to meet the AMR challenge

This issue of the New Zealand Veterinary Journal focuses on antimicrobial resistance (AMR), because of its rising prevalence, its impact on morbidity and mortality, and uncertainty about our ability to continue to treat infections effectively into the future. While AMR genes are not of our making, the rise in prevalence of AMR, predicted since antibiotics were first used (Finland et al. 1946; Jawetz 1963), is undoubtedly anthropogenic. However the complexity of the relationships between antimicrobial use and resistance, and their impact on ecosystems including the humans and animals that inhabit them, makes AMR one of health’s “wicked problems” (Rittel and Webber 1973; Signal et al. 2013). In order to understand how best to respond to this problem, we need to pay attention to the complex systems that underpin it, in order to understand how best to respond.

Antistaphylococcal β-Lactams versus Vancomycin for Treatment of Infective Endocarditis Due to Methicillin-Susceptible Coagulase-Negative Staphylococci: a Prospective Cohort Study from the International Collaboration on Endocarditis

ABSTRACT The phenotypic expression of methicillin resistance among coagulase-negative staphylococci (CoNS) is heterogeneous regardless of the presence of the mecA gene. The potential discordance between phenotypic and genotypic results has led to the use of vancomycin for the treatment of CoNS infective endocarditis (IE) regardless of methicillin MIC values. In this study, we assessed the outcome of methicillin-susceptible CoNS IE among patients treated with antistaphylococcal β-lactams (ASB) versus vancomycin (VAN) in a multicenter cohort study based on data from the International Collaboration on Endocarditis (ICE) Prospective Cohort Study (PCS) and the ICE-Plus databases. The ICE-PCS database contains prospective data on 5,568 patients with IE collected between 2000 and 2006, while the ICE-Plus database contains prospective data on 2,019 patients with IE collected between 2008 and 2012. The primary endpoint was in-hospital mortality. Secondary endpoints were 6-month mortality and survival time. Of the 7,587 patients in the two databases, there were 280 patients with methicillin-susceptible CoNS IE. Detailed treatment and outcome data were available for 180 patients. Eighty-eight patients received ASB, while 36 were treated with VAN. In-hospital mortality (19.3% versus 11.1%; P = 0.27), 6-month mortality (31.6% versus 25.9%; P = 0.58), and survival time after discharge (P = 0.26) did not significantly differ between the two cohorts. Cox regression analysis did not show any significant association between ASB use and the survival time (hazard ratio, 1.7; P = 0.22); this result was not affected by adjustment for confounders. This study provides no evidence for a difference in outcome with the use of VAN versus ASB for methicillin-susceptible CoNS IE.