Publications by authors named "Timothy D Planche"

6 Publications

  • Page 1 of 1

Anti-bacterial antibodies in multiple myeloma patients at disease presentation, in response to therapy and in remission: implications for patient management.

Blood Cancer J 2020 11 4;10(11):114. Epub 2020 Nov 4.

Institute of Immunology and Immunotherapy, Clinical Immunology Service, University of Birmingham, Birmingham, UK.

Multiple myeloma (MM) is associated with increased risk of infection, but little is known regarding antibody levels against specific bacteria. We assessed levels of polyclonal immunoglobulin and antibacterial antibodies in patients recruited to the TEAMM trial, a randomised trial of antibiotic prophylaxis at the start of anti-myeloma treatment. Polyclonal IgG, IgA and IgM levels were below the reference range in 71%, 83% and 90% of 838 MM patients at diagnosis. Anti-vaccine targeted tetanus toxoid antibodies were protective in 95% of 193 healthy controls but only 41% of myeloma patients. In healthy controls, protective antibodies against 6/12 pneumococcal serotypes, haemophilus and meningococcus A were present in 67%, 41% and 56% compared to just 15%, 21% and 17% of myeloma patients. By 1 year, myeloma patients IgG levels had recovered for 57% of patients whilst the proportion with protective levels of IgG against thymus-dependent protein antigen tetanus toxoid had changed little. In contrast the proportions of patients with protective levels against thymus independent polysaccharide antigens pneumococcus, haemophilus and meningococcus had fallen from 15 to 7%, 21 to 0% and 17 to 11%. Findings highlight the need for strategies to protect patients against bacterial infections during therapy and vaccination programmes during remission.
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http://dx.doi.org/10.1038/s41408-020-00370-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642409PMC
November 2020

The Epidemiology of Community Clostridium difficile Infection: A Five-Year Population-Based Study on the Bailiwick of Jersey, Channel Islands.

Infect Control Hosp Epidemiol 2018 05 27;39(5):603-607. Epub 2018 Feb 27.

2Institute of Infection and Immunity,St George's University of London,London,United Kingdom.

We studied healthcare-associated and community-associated Clostridium difficile infection (CDI) in Jersey, Channel Islands (2008-2012). The Island's stable population has reliable denominator data, a clearly defined at-risk population, and healthcare contact that is easily followed. The vast majority of CDI cases had had recent healthcare contact, and true community-associated disease is extremely rare.Infect Control Hosp Epidemiol 2018;39:603-607.
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http://dx.doi.org/10.1017/ice.2018.38DOI Listing
May 2018

Neonatal gram-negative infections, antibiotic susceptibility and clinical outcome: an observational study.

Arch Dis Child Fetal Neonatal Ed 2016 Nov 7;101(6):F507-F512. Epub 2016 Mar 7.

Paediatric Infectious Disease Research Group, St George's, University of London, London, UK.

Background: Neonatal gram-negative (GN) infections are associated with high mortality and morbidity. Early appropriate antibiotic treatment is vital and gentamicin is the most frequently used antibiotic on neonatal units (NNUs). Antimicrobial breakpoints are predominantly based on adult data and the relationship between minimum inhibitory concentrations (MICs) and outcome in neonates is unclear. We aimed to determine the MIC of GN pathogens causing neonatal infections and relate this to clinical outcomes.

Methods: MICs for eight antibiotics plus extended spectrum β-lactamase (ESBL) production were determined for invasive GN bacterial isolates from eight UK NNUs. European Committee on Antimicrobial Susceptibility Testing breakpoints were applied. MIC was correlated with clinical outcome using multivariable regression analysis.

Results: 118 isolates from 116 patients were analysed. The median birth gestation and postnatal age was 27 weeks (IQR 24.6-32.3) and 20 days (IQR 5-44), respectively. Pathogens included (51%), spp (23%) and spp (22%). 10-day attributable mortality was 18.1% (21 patients) with the highest mortality from infections. ESBL producers accounted for 13.8% of the isolates. In regression analysis, increasing gentamicin MIC was associated with increased mortality in gentamicin treated patients across the full MIC range (OR per log increase in MIC: 2.29; 95% CI 1.23 to 4.26, p=0.009), including susceptible isolates only (MIC ≤4) (OR 3.05; 95% CI 1.10 to 8.46, p=0.032).

Conclusions: Neonatal mortality from GN infections remains high and is associated with increasing gentamicin MIC, even for isolates deemed susceptible. A better understanding of population-specific MICs and aminoglycoside dosing is required to guide empiric antibiotic treatment.
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http://dx.doi.org/10.1136/archdischild-2015-309554DOI Listing
November 2016

High-Resolution Analysis by Whole-Genome Sequencing of an International Lineage (Sequence Type 111) of Pseudomonas aeruginosa Associated with Metallo-Carbapenemases in the United Kingdom.

J Clin Microbiol 2015 Aug 3;53(8):2622-31. Epub 2015 Jun 3.

Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, Public Health England, Colindale, London, United Kingdom.

Whole-genome sequencing (WGS) was carried out on 87 isolates of sequence type 111 (ST-111) of Pseudomonas aeruginosa collected between 2005 and 2014 from 65 patients and 12 environmental isolates from 24 hospital laboratories across the United Kingdom on an Illumina HiSeq instrument. Most isolates (73) carried VIM-2, but others carried IMP-1 or IMP-13 (5) or NDM-1 (1); one isolate had VIM-2 and IMP-18, and 7 carried no metallo-beta-lactamase (MBL) gene. Single nucleotide polymorphism analysis divided the isolates into distinct clusters; the NDM-1 isolate was an outlier, and the IMP isolates and 6/7 MBL-negative isolates clustered separately from the main set of 73 VIM-2 isolates. Within the VIM-2 set, there were at least 3 distinct clusters, including a tightly clustered set of isolates from 3 hospital laboratories consistent with an outbreak from a single introduction that was quickly brought under control and a much broader set dominated by isolates from a long-running outbreak in a London hospital likely seeded from an environmental source, requiring different control measures; isolates from 7 other hospital laboratories in London and southeast England were also included. Bayesian evolutionary analysis indicated that all the isolates shared a common ancestor dating back ∼50 years (1960s), with the main VIM-2 set separating approximately 20 to 30 years ago. Accessory gene profiling revealed blocks of genes associated with particular clusters, with some having high similarity (≥95%) to bacteriophage genes. WGS of widely found international lineages such as ST-111 provides the necessary resolution to inform epidemiological investigations and intervention policies.
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http://dx.doi.org/10.1128/JCM.00505-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4508460PMC
August 2015

Differences in outcome according to Clostridium difficile testing method: a prospective multicentre diagnostic validation study of C difficile infection.

Lancet Infect Dis 2013 Nov 3;13(11):936-45. Epub 2013 Sep 3.

Centre for Infection and Immunity, Division of Clinical Medicine, St George's, University of London, London, UK; Department of Medical Microbiology, St George's Healthcare NHS Trust, London, UK.

Background: Diagnosis of Clostridium difficile infection is controversial because of many laboratory methods, compounded by two reference methods. Cytotoxigenic culture detects toxigenic C difficile and gives a positive result more frequently (eg, because of colonisation, which means that individuals can have the bacterium but no free toxin) than does the cytotoxin assay, which detects preformed toxin in faeces. We aimed to validate the reference methods according to clinical outcomes and to derive an optimum laboratory diagnostic algorithm for C difficile infection.

Methods: In this prospective, multicentre study, we did cytotoxigenic culture and cytotoxin assays on 12,420 faecal samples in four UK laboratories. We also performed tests that represent the three main targets for C difficile detection: bacterium (glutamate dehydrogenase), toxins, or toxin genes. We used routine blood test results, length of hospital stay, and 30-day mortality to clinically validate the reference methods. Data were categorised by reference method result: group 1, cytotoxin assay positive; group 2, cytotoxigenic culture positive and cytotoxin assay negative; and group 3, both reference methods negative.

Findings: Clinical and reference assay data were available for 6522 inpatient episodes. On univariate analysis, mortality was significantly higher in group 1 than in group 2 (72/435 [16·6%] vs 20/207 [9·7%], p=0·044) and in group 3 (503/5880 [8·6%], p<0·001), but not in group 2 compared with group 3 (p=0·4). A multivariate analysis accounting for potential confounders confirmed the mortality differences between groups 1 and 3 (OR 1·61, 95% CI 1·12-2·31). Multistage algorithms performed better than did standalone assays.

Interpretation: We noted no increase in mortality when toxigenic C difficile alone was present. Toxin (cytotoxin assay) positivity correlated with clinical outcome, and so this reference method best defines true cases of C difficile infection. A new diagnostic category of potential C difficile excretor (cytotoxigenic culture positive but cytotoxin assay negative) could be used to characterise patients with diarrhoea that is probably not due to C difficile infection, but who can cause cross-infection.
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http://dx.doi.org/10.1016/S1473-3099(13)70200-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3822406PMC
November 2013