Effects of postage on recovery of pathogens from cystic fibrosis sputum samples.

BACKGROUND: Regular surveillance microbiology of sputum is used in cystic fibrosis (CF) to monitor for new pathogens and target treatments. A move to remote clinics has meant greater reliance on samples collected at home and posted back. The impact of delays and sample disruption caused by posting has not been systematically assessed but could have significant implications for CF microbiology. METHODS: Sputum samples collected from adult CF patients were mixed, split, and either processed immediately or posted back to laboratory. Processing involved a further split into aliquots for culture-dependant and-independent microbiology (quantitative PCR [QPCR] and microbiota sequencing). We calculated retrieval by both approaches for five typical CF pathogens: Pseudomonas aeruginosa, Burkholderia cepacia complex, Achromobacter xylosoxidans, Staphylococcus aureus and Stenotrophomonas maltophilia. RESULTS: 93 paired samples were collected from 73 CF patients. Median interval between sample posting and receipt was 5 days (range 1-10). For culture, overall concordance for posted and fresh samples was 86% across the five targeted pathogens (ranging from 57 to 100% for different organisms), with no bias towards either sample type. For QPCR, overall concordance was 62% (range 39-84%), again with no bias towards fresh or posted samples. There were no significant differences in culture or QPCR for samples with short (≤3days) versus extended (≥7days) postal delays. Posting had no significant impact on pathogen abundance nor on microbiota characteristics. CONCLUSIONS: Posted sputum samples reliably reproduced culture-based and molecular microbiology of freshly collected samples, even after prolonged delays at ambient conditions. This supports use of posted samples during remote monitoring.

Open extent IV thoracoabdominal aneurysm repair: 22-year experience of the Scottish National Service.

BACKGROUND: Since 1999, the Scottish National Service for Thoracoabdominal Aneurysms has offered repair of thoracoabdominal aneurysms (TAAAs) to a population of 5.5 million people. The open operation most commonly performed by the service is the extent IV TAAA repair. METHODS: All extent IV open TAAA repairs performed at the Scottish National Service for TAAAs from June 1999 until April 2021 were evaluated for clinical features, technical details, and clinical outcomes. The primary outcome measure was 30-day mortality; secondary outcomes included short-term (90 days, 6 months, 1 and 2 years) and long-term (5 and 10 years) survival, perioperative complications, and reintervention. Survival was assessed using Kaplan-Meier analysis. RESULTS: Some 248 patients underwent extent IV TAAA repair, with elective surgery in 204 (82.3 per cent). A totally abdominal transperitoneal approach was used for all patients, with a median visceral ischaemia time of 40 (i.q.r. 35-48) min. Overall, 18 patients (7.3 per cent) died within 30 days. The proportion of patients surviving at 90 days, 6 months, 1, 2, 5, and 10 years was 0.91, 0.90, 0.89, 0.85, 0.72, and 0.41, respectively. Ten patients (4.0 per cent) required a reintervention while in hospital, four (1.6 per cent) experienced permanent spinal cord ischaemia, 19 (7.9 per cent) required temporary renal replacement therapy (RRT), and four (1.6 per cent) required permanent RRT. CONCLUSION: Open extent IV TAAA repair performed in a high-volume national centre is associated with favourable short- and long-term survival, and acceptable complication rates.

Evaluation of in vitro activity of fosfomycin, and synergy in combination, in Gram-negative bloodstream infection isolates in a UK teaching hospital.

Introduction. Fosfomycin has retained activity against many multi-drug resistant (MDR) Gram-negatives, and may be useful against extended spectrum beta-lactamase (ESBL) producing and carbapenem-resistant Enterobacterales to improve clinical outcomes.Hypothesis/Gap Statement. There are few data from the UK on the susceptibility of invasive Gram-negative isolates to fosfomycin, especially in the era of increasing use of oral fosfomycin for urinary tract infections (UTIs).Aim. We evaluated fosfomycin susceptibility against 100 consecutive Gram-negative bloodstream isolates, both individually, and in combination with other mechanistically similar and differing antibiotics. The aim was to investigate the synergy between antibiotic combinations against several E. coli, K. pneumoniae and P. aeruginosa isolates with variable levels of resistance.Methodology. Disc diffusion and MIC test strip methods applying revised EUCAST guidelines for Fosfomycin were used, followed by the MTS™ 'cross synergy' method for 'resistant' isolates as defined below: (a) Fosfomycin resistant by MIC test strip; (b) MDR isolates defined as being resistant to ≥3 classes of antibiotics (based on routine sensitivity testing; beta lactams were considered as a single class), and/or (c) AMP C or ESBL or carbapenemase producers (or carbapenem resistant). FIC Index (Fractional Inhibitory Concentration Index) calculations were used to interpret findings, whereby: FIC = (MICA combination A+B/ MIC agent A) + (MICB combination A+B/ MIC agent B). A result of ≤0.5 was taken to indicate 'synergy', >0.5 and ≤1.0 to indicate 'additive' effect, >1.0 and ≤4.0 to indicate 'indifference', and >4.0 to indicate 'antagonism'.Results. We found that 95/100 isolates were susceptible to fosfomycin by MIC test strip, with 88/100 isolates susceptible to fosfomycin by disc, based on EUCAST guideline breakpoints. A total of 30/100 isolates (the more 'resistant' of the 100) were eligible for synergy testing according to our definitions (see Methodology), with the remaining 70 isolates not tested further. Seventeen out of 30 were MDR, 2/30 were AMP C producers and 9/30 were ESBL producers. Overall, 34/300 (11 %) of all combination tests showed synergy and 161/300 (54 %) were additive. Synergy was most commonly detected between fosfomycin and beta-lactam antibiotics, including piperacillin/tazobactam (10/30; 33 %), ceftazidime/avibactam (10/30; 30 %), and temocillin (8/30; 27 %). An additive effect was most commonly detected with aztreonam (25/30; 83 %) and meropenem (25/30; 83 %), but 100 % indifference was found with tigecycline (30/30). No antagonism was identified with any antibiotic combination.Conclusion. Fosfomycin non-susceptibility by MIC test strip was unusual. Synergy was variable when combining fosfomycin with other antibiotics against the more 'resistant' isolates. Synergistic/additive effects were detected for beta-lactam/fosfomycin combinations in >80 % of all such combinations, suggesting beta-lactams may be the preferred partner for fosfomycin. Agents with a discordant site of action were more likely to result in indifference. Antagonism was not detected.

Selective transperineal prostate biopsy for fluoroquinolone-resistance patients reduces sepsis and cost.

BACKGROUND: Urosepsis is a recognized complication of transrectal ultrasound-guided prostate biopsy (TRUS-Bx). Pre-biopsy rectal swabs have been used to identify patients with microorganisms in the rectal flora resistant to the conventionally used empirical prophylaxis. The transperineal route of biopsy (TP-Bx) has a lower complication risk but comes at an increased cost. MATERIALS AND METHODS: Retrospective cohort study including patients undergoing prostate biopsies between October/2015 and April/2018. The intervention cohort, a rectal swab was performed, the result of which dictated the biopsy route; TRUS-Bx against TP-Bx. TP-Bx for patients with fluoroquinolone resistance or extended-spectrum ß-lactamase. The control cohort underwent TRUS without a rectal swab receiving empirical antibiotics-oral ciprofloxacin and intravenous gentamicin. RESULTS: Total 1000 patients were included in which 500 underwent a swab, 14 (2.8%) developed post-TRUS biopsy infective complications with 3 having positive bacteremia (0.6%); 500 had no swab, 47 (9.4%) developed post-TRUS biopsy infective complications with 22 (4.4%, p < 0.05) having positive bacteremia. Three patients (0.6%) of patients who underwent swab developed urinary tract infection symptoms whilst 12 (2.4%) had urinary tract infection in the control group. In those patients that underwent a swab, 14 required hospitalization with mean length of stay of 2.5 days versus 43 patients of the control with 3.6 days. Cost analysis concluded savings of this strategy was £18,711. CONCLUSIONS: We have demonstrated a protocol that reserves template biopsies for higher risk patients and can significantly reduce sepsis and other infectious complication rates whilst also proving to be a cost-efficient strategy. We recommend that units not utilizing rectal swabs to uncover the fluoroquinolone resistance rate by introducing them. We advocate units that already utilize rectal swabs, to introduce transperineal biopsy for their higher risk patients.

A prospective surveillance study to determine the prevalence of 16S rRNA methyltransferase-producing Gram-negative bacteria in the UK.

OBJECTIVES: To determine the prevalence of 16S rRNA methyltransferase- (16S RMTase-) producing Gram-negative bacteria in patients in the UK and to identify potential risk factors for their acquisition. METHODS: A 6 month prospective surveillance study was conducted from 1 May to 31 October 2016, wherein 14 hospital laboratories submitted Acinetobacter baumannii, Enterobacterales and Pseudomonas aeruginosa isolates that displayed high-level amikacin resistance according to their testing methods, e.g. no zone of inhibition with amikacin discs. Isolates were linked to patient travel history, medical care abroad, and previous antibiotic exposure using a surveillance questionnaire. In the reference laboratory, isolates confirmed to grow on Mueller-Hinton agar supplemented with 256 mg/L amikacin were screened by PCR for 16S RMTase genes armA, rmtA-rmtH and npmA, and carbapenemase genes (blaKPC, blaNDM, blaOXA-48-like and blaVIM). STs and total antibiotic resistance gene complement were determined via WGS. Prevalence was determined using denominators for each bacterial species provided by participating hospital laboratories. RESULTS: Eighty-four isolates (44.7%), among 188 submitted isolates, exhibited high-level amikacin resistance (MIC >256 mg/L), and 79 (94.0%) of these harboured 16S RMTase genes. armA (54.4%, 43/79) was the most common, followed by rmtB (17.7%, 14/79), rmtF (13.9%, 11/79), rmtC (12.7%, 10/79) and armA + rmtF (1.3%, 1/79). The overall period prevalence of 16S RMTase-producing Gram-negative bacteria was 0.1% (79/71 063). Potential risk factors identified through multivariate statistical analysis included being male and polymyxin use. CONCLUSIONS: The UK prevalence of 16S RMTase-producing Gram-negative bacteria is low, but continued surveillance is needed to monitor their spread and inform intervention strategies.

Screening for Candida auris in patients admitted to eight intensive care units in England, 2017 to 2018.

BackgroundCandida auris is an emerging multidrug-resistant fungal pathogen associated with bloodstream, wound and other infections, especially in critically ill patients. C. auris carriage is persistent and is difficult to eradicate from the hospital environment.AimWe aimed to pilot admission screening for C. auris in intensive care units (ICUs) in England to estimate prevalence in the ICU population and to inform public health guidance.MethodsBetween May 2017 and April 2018, we screened admissions to eight adult ICUs in hospitals with no previous cases of C. auris, in three major cities. Swabs were taken from the nose, throat, axilla, groin, perineum, rectum and catheter urine, then cultured and identified using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). Patient records were linked to routine ICU data to describe and compare the demographic and health indicators of the screened cohort with a national cohort of ICU patients admitted between 2016 and 2017.ResultsAll C. auris screens for 921 adults from 998 admissions were negative. The upper confidence limit of the pooled prevalence across all sites was 0.4%. Comparison of the screened cohort with the national cohort showed it was broadly similar to the national cohort with respect to demographics and co-morbidities.ConclusionThese findings imply that C. auris colonisation among patients admitted to ICUs in England is currently rare. We would not currently recommend widespread screening for C. auris in ICUs in England. Hospitals should continue to screen high-risk individuals based on local risk assessment.

Reducing the risk of venous thromboembolism following superficial endovenous treatment: A UK and Republic of Ireland consensus study.

OBJECTIVES: Venous thromboembolism is a potentially fatal complication of superficial endovenous treatment. Proper risk assessment and thromboprophylaxis could mitigate this hazard; however, there are currently no evidence-based or consensus guidelines. This study surveyed UK and Republic of Ireland vascular consultants to determine areas of consensus. METHODS: A 32-item survey was sent to vascular consultants via the Vascular and Endovascular Research Network (phase 1). These results generated 10 consensus statements which were redistributed (phase 2). 'Good' and 'very good' consensus were defined as endorsement/rejection of statements by >67% and >85% of respondents, respectively. RESULTS: Forty-two consultants completed phase 1. This generated seven statements regarding risk factors mandating peri-procedural pharmacoprophylaxis and three statements regarding specific pharmacoprophylaxis regimes. Forty-seven consultants completed phase 2. Regarding venous thromboembolism risk factors mandating pharmacoprophylaxis, 'good' and 'very good' consensus was achieved for 5/7 and 2/7 statements, respectively. Regarding specific regimens, 'very good' consensus was achieved for 3/3 statements. CONCLUSIONS: The main findings from this study were that there was 'good' or 'very good' consensus that patients with any of the seven surveyed risk factors should be given pharmacoprophylaxis with low-molecular-weight heparin. High-risk patients should receive one to two weeks of pharmacoprophylaxis rather than a single dose.

Sixty-eight consecutive patients assessed for COVID-19 infection: Experience from a UK Regional infectious diseases Unit.

BACKGROUND: Assessment of possible infection with SARS-CoV-2, the novel coronavirus responsible for COVID-19 illness, has been a major activity of infection services since the first reports of cases in December 2019. OBJECTIVES: We report a series of 68 patients assessed at a Regional Infection Unit in the UK. METHODS: Between 29 January 2020 and 24 February 2020, demographic, clinical, epidemiological and laboratory data were collected. We compared clinical features between patients not requiring admission for clinical reasons or antimicrobials with those assessed as needing either admission or antimicrobial treatment. RESULTS: Patients assessed were aged from 0 to 76 years; 36/68 were female. Peaks of clinical assessments coincided with updates to the case definition for suspected COVID-19. Microbiological diagnoses included SARS-CoV-2, mycoplasma pneumonia, influenza A, non-SARS/MERS coronaviruses and rhinovirus/enterovirus. Nine of sixty-eight received antimicrobials, 15/68 were admitted, 5 due to inability to self-isolate. Patients requiring admission on clinical grounds or antimicrobials (14/68) were more likely to have fever or raised respiratory rate compared to those not requiring admission or antimicrobials. CONCLUSIONS: The majority of patients had mild illness, which did not require clinical intervention. This finding supports a community testing approach, supported by clinicians able to review more unwell patients. Extensions of the epidemiological criteria for the case definition of suspected COVID-19 lead to increased screening intensity; strategies must be in place to accommodate this in time for forthcoming changes as the epidemic develops.

Investigation of a Pandoraea apista cluster common to adult and paediatric cystic fibrosis patients attending two hospitals in the same city.

PURPOSE: We examined evidence for transmission of Pandorea apista among cystic fibrosis (CF) patients attending paediatric and adult services in one city who had previously been found to harbour related isolates by pulsed-field gel electrophoresis (PFGE). METHODOLOGY: The whole-genome sequences of 18 isolates from this cluster from 15 CF patients were examined, along with 2 cluster isolates from 2 other centres. The annotated sequence of one of these, Pa14367, was examined for virulence factors and antibiotic resistance-associated genes in comparison with data from a 'non-cluster' isolate, Pa16226. RESULTS: Single-nucleotide polymorphism (SNP) analysis suggested that cluster isolates from the same city differed from one another by a minimum of 1 and a maximum of 383 SNPs (an average of 213 SNPs; standard deviation: 18.5), while isolates from the 2 other hospitals differed from these by a minimum of 34 and 61 SNPs, respectively. Pa16226 differed from all cluster isolates by a minimum of 22 706 SNPs. Evidence for patient-to-patient transmission among isolates from the same city was relatively limited, although transmission from a common source could not be excluded. The annotated genomes of Pa14367 and Pa16226 carried putative integrative and conjugative elements (ICEs), coding for type IV secretion systems, and genes associated with heavy metal degradation and carbon dioxide fixation, and a wide selection of genes coding for efflux pumps, beta-lactamases and penicillin-binding proteins. CONCLUSION: Epidemiological analysis suggested that this cluster could not always be attributed to patient-to-patient transmission. The acquisition of ICE-related virulence factors may have had an impact on its prevalence.

rpoB gene sequencing highlights the prevalence of an E. miricola cluster over other Elizabethkingia species among UK cystic fibrosis patients.

Difficulties in distinguishing species of the Elizabethkingia genus by MALDI-TOF prompted use of rpoB sequencing to investigate species distribution among 44 isolates from cystic fibrosis (CF) patients. Forty-three isolates from 38 patients formed a cluster comprising E. miricola and proposed novel species E. bruuniana sp. nov., the exception clustering with proposed species E. ursingii sp. nov., also part of this wider cluster. All 44 isolates were PCR-positive for urease gene ureG, whereas only one of 23 E. anophelis isolates from non-CF patients was positive, suggesting that this gene is largely associated with the E. miricola cluster. Antibiotic susceptibilities of 12 CF isolates revealed all were resistant to beta-lactams with the exception of piperacillin-tazobactam, and were only susceptible to minocycline and co-trimoxazole. Pulsed-field gel electrophoresis analysis revealed 4 shared strains among 17 CF patients in one pediatric clinic, but epidemiological investigations did not support patient-to-patient transmission except between one sibling pair.

Early diagnosis of cardiac implantable electronic device generator pocket infection using ¹8F-FDG-PET/CT.

AIMS: To examine the utility of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in the early diagnosis of cardiac implantable electronic device (CIED) generator pocket infection. METHODS AND RESULTS: A total of 86 patients with CIEDs were evaluated with (18)F-FDG PET/CT imaging: 46 with suspected generator pocket infection and 40 without any history of infection. (18)F-FDG activity in the region of the generator pocket was expressed as a semi-quantitative ratio (SQR)-defined as the maximum count rate around the CIED divided by the mean count rate between normal right and left lung parenchyma. All patients underwent standard clinical management, independent of the PET/CT result. Patients with suspected generator pocket infection that required CIED extraction (n = 32) had significantly higher (18)F-FDG activity compared with those that did not (n = 14), and compared with controls (n = 40) [SQR: 4.80 (3.18-7.05) vs. 1.40 (0.88-1.73) vs. 1.10 (0.98-1.40), respectively; P < 0.001]. On receiver operator characteristic analysis, SQR had a high diagnostic accuracy (area under curve = 0.98) for the early identification of patients with confirmed infection (i.e. those ultimately needing extraction)-with an optimal SQR cut-off value of >2.0 (sensitivity = 97%; specificity = 98%). CONCLUSION: This study highlights the potential benefits of evaluating patients with suspected CIED generator pocket infection using (18)F-FDG PET/CT. In this study, (18)F-FDG PET/CT had a high diagnostic accuracy in the early diagnosis of CIED generator pocket infection, even where initial clinical signs were underwhelming.

Brucella melitensis sternal osteomyelitis following median sternotomy.

Human brucellosis, a zoonotic infection, may present with a range of symptoms but is rarely described as a cause of surgical site infections. We present the first reported case of Brucella melitensis causing sternal osteomyelitis of a midline sternotomy for a coronary artery bypass graft. The operation was performed in a non-endemic country but the patient had travelled to Syria immediately before surgery, where the infection was assumed to have been acquired. The infection resolved following treatment with doxycycline, rifampicin and gentamicin. We review the literature for surgical site infections related to Brucella species and discuss the infection control implications. Human brucellosis has the potential to cause surgical site infections and it should be in the differential diagnosis of any patient with a relevant exposure history presenting with a febrile illness and musculoskeletal findings.