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IntroductionSeveral viral respiratory infections - notably influenza - are associated with secondary bacterial infection and additional pathology. The extent to which this applies for COVID-19 is unknown. Accordingly, we aimed to define the bacteria causing secondary pneumonias in COVID-19 ICU patients using the FilmArray Pneumonia Panel, and to determine this test’s potential in COVID-19 management.MethodsCOVID-19 ICU patients with clinically-suspected secondary infection at 5 UK hospitals were tested with the FilmArray at point of care. We collected patient demographic data and compared FilmArray results with routine culture.ResultsWe report results of 110 FilmArray tests on 94 patients (16 had 2 tests): 69 patients (73%) were male, the median age was 59 yrs; 92 were ventilated. Median hospital stay before testing was 14 days (range 1-38). Fifty-nine (54%) tests were positive, with 141 bacteria detected. Most were Enterobacterales (n=55, includingKlebsiellaspp. [n= 35]) orStaphylococcus aureus(n=13), as is typical of hospital and ventilator pneumonia. Community pathogens, includingHaemophilus influenzae(n=8) andStreptococcus pneumoniae(n=1), were rarer. FilmArray detected one additional virus (Rhinovirus/Enterovirus) and no atypical bacteria. Fewer samples (28 % vs. 54%) were positive by routine culture, and fewer species were reported per sample;Klebsiellaspecies remained the most prevalent pathogens.ConclusionFilmArray had a higher diagnostic yield than culture for ICU COVID-19 patients with suspected secondary pneumonias. The bacteria found mostly were Enterobacterales,S. aureusandP. aeruginosa, as in typical HAP/VAP, but withKlebsiellaspp. more prominent. We found almost no viral co-infection. Turnaround from sample to results is around 1h 15 min compared with the usual 72h for culture, giving prescribers earlier data to inform antimicrobial decisions.

Introduction Meropenem is a broad spectrum antibiotic used to treat a variety of bacterial infections. There are no clear standards nationally for the use of meropenem. The purpose of this study is to audit the appropriateness of Meropenem prescription at West Hertfordshire NHS trust METHODOLOGY Patients started on meropenem were identified via the hospital pharmacy in the period from 1st January 2019 to 31st March 2019. Patients’ clinical notes, drug charts and blood tests were reviewed. Appropriateness of meropenem prescription was judged based on the following: indication, penicillin allergy and its nature, pathogen antibiogram, microbiologists approval, indications for escalation and duration of treatment RESULTS forty-eight patients were identified during the study period. The main indications were hospital-acquired/community-acquired pneumonia and UTI. Penicillin allergy was documented in 31%, the nature of allergy was intolerance in 13% and not known in 20%. Of note, in 42% of these, treatment was not pathogen guided. In 45.5% of non-penicillin allergic patients, escalation to meropenem were neither supported by antibiogram nor by microbiologists. The main driver was raised inflammatory markers (62.5%). Of the 37 patients who completed their treatment during the study period, 21.6% had > 7 days with only 50% recommended by Microbiologists. CONCLUSION: In third of the patients, meropenem use was driven by penicillin allergy, however the nature of allergy did not justify its use in many of these cases. Lack of microbiology approval, failure to de-escalate and long courses of meropenem were additional areas identified to target in our antimicrobial stewardship programme

Since the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), millions have been diagnosed with COVID-19. The major clinical manifestations of SARS-CoV-2 infection are pulmonary, however reports of COVID-19-associated central nervous system complications emerged.1 2 We report a case of encephalitis in a pulmonologically asymptomatic patient with COVID-19. A 66-year-old female presented in mid-March 2020, with a few hours history of confusion. She was completely well until the day of admission. There was no medical, infectious or behavioural prodrome. There was no alcohol or nutritional history. She had travelled to Spain, the USA and Mexico in the 3 months prior, but had been home for 19 days. She suddenly complained that her head ‘felt funny’. She carried on normal tasks but, within an hour, became confused, amnestic and was unaware of why social distancing measures were being observed. On admission, her temperature was 37.9°C. Other observations were normal. She was lymphopaenic at 0.4×109/L (0.8–3.1). Full blood count was otherwise normal. C-reactive protein (CRP) was 14.5 mg/L (0–5). Routine blood tests, including renal function, liver function and clotting, were normal. A brain CT was unremarkable. Six hours after admission, she had a single, spontaneously resolving, generalised tonic-clonic seizure. Her postictal Glasgow Coma Scale (GCS) was 6/15 (E1/V1/M4). This remained unchanged for 48 hours. Postictal neurological examination showed equal, reactive pupils, no response to visual menace, no vestibulo-ocular reflex, normal tone bilaterally, symmetrical brisk reflexes and extensor plantars. She remained febrile (37.9°C) for 48 hours. Oxygen saturation dropped to 93% on air only once during her 4-week admission. She never developed breathlessness, cough or tachypnoea. An MRI of the brain on day 2 showed non-enhancing, symmetrical T2 and FLAIR …

Arteriovenous fistula (AVF) is the preferred access for hemodialysis (HD). Buttonhole (BH) needling has increased following the introduction of "blunt" fistula needles. Although some reported advantages for BH needling, others have reported increased infection risk. As such we reviewed our center practice, and the effect of both nasal screening and eradication and re-education and training programs. We audited the outcomes of 881 HD patients dialyzed between November 2009 and May 2012, divided into three groups: 175 dialyzing exclusively by central venous catheter (CVC), 478 exclusively by area needling AVF (AVF) and 219 by BH. There were 31 Staphylococcus aureus bacteremias (SABs); 14 (45.2%) dialyzing with CVCs, 12 (38.7%) BH and five (16.1%) AVF. The 30 day mortality rate for SAB was 7.5% with a complication rate of 22.6%. The hazard ratio for first SAB was significantly greater for both CVC and BH access compared to AVF (5.3 (95% CI -1.9-18.6), P

Xenogeneic anti-lymphocyte serum (ALS) remains a major reagent for immunosuppression in clinical practice, but mechanisms of action and risks of opportunistic infection have not been considered in the context of innate immunity and its role in immune responsiveness. Rabbit anti rat ALS was administered intraperitoneally. Blood was taken for flow cytometry to establish absolute counts of leucocyte subsets. Tissues were harvested for immunohistology to evaluate interstitial dendritic cells and tissue macrophages. At day 2 of ALS therapy, T cells are completely depleted, as anticipated. B cells are undiminished and form approximately 90% of blood leucocytes. Monocytes and natural killer (NK) cells are substantially (approximately 80%), but not completely, depleted, and there is a trend for diminished numbers of putative dendritic cells. Neither interstitial dendritic cells nor tissue macrophages in heart are affected. The results at day 7 were very similar to day 2. Substantial depletion of blood monocytes and NK cells might attenuate the innate immune system, and represent a possible supplementary mechanism (in addition to T cell depletion) for suppression of rejection. It might be of particular importance in reducing defences against infections. Monitoring these parameters could be of clinical value.

Buttonhole needling for arteriovenous fistulae (AVF) has increased in popularity among dialysis centers. Concerns have been raised about the risks of infection, so we reviewed our experience of buttonhole needling in 227 adult patients on hemodialysis. The mean buttonhole AVF survival was 27.0 months, in 227 patients, 61.1% male, mean age 63.8 ± 15.5 years, 45.8% with diabetes mellitus, median dialysis vintage 19 months (6.5-42.8). Ninety-six patients transferred to rope ladder AVF cannulation, because of cannulation failure in 25%, persistent bleeding at the needling site in 24%, fistula thrombosis in 14%, and infections in 15%. Because of persistent methicillin-sensitive Staphylococcus aureus (MSSA) or methicillin-resistant S. aureus (MRSA) colonization, 18.8% discontinued buttonhole needling. Transfer from buttonhole needling was more common for people with diabetes (X = 6.57; p = 0.035), older patients (odds ratio, 0.985; p = 0.007), and persistent MSSA/MRSA colonization (odds ratio, 0.88; p = 0.037). Eleven episodes of suspected buttonhole S. aureus bacteremia occurred giving a bacteremia rate of 2.94 per 100 patient years, and 15 local infections giving an infection rate of 4.01 per 100 patient years. In this large series of buttonhole AVF access, although infection rates were increased, more patients discontinued buttonhole needling because of technical cannulation problems and persistent bleeding from needle tracks.

Angiogenesis is thought to play a major role in the development of Kaposi's sarcoma (KS), considered by many to be a hyperplastic disorder caused in part by local production of inflammatory cytokines. The antiangiogenic effects of protease inhibitors, in particular ritonavir, have been suggested in laboratory work to lead to regression of KS, and recent data have shown the importance of ritonavir as a model of pharmaceutical development. As our clinical cohort data has shown that non-nucleoside reverse transcriptase inhibitor-based regimens are not inferior to protease inhibitor-based therapy in the prevention of KS, we investigated the specific contribution of ritonavir to chemoprevention of this AIDS-defining illness. In a logistic regression analysis, we found that ritonavir-based therapy confers no advantages compared to other regimens in the prevention of KS. This is consistent with data suggesting that regression of KS is mediated by an overall improvement in immune function and not by the effects of specific antiretrovirals.

Pasteurella multocida is a rare cause of infective endocarditis with only a few cases described. This report involves a 38-year-old penicillin-allergic patient in an immunocompromised state with several co-morbidities. Two molecular microbiological techniques, 16S rRNA sequencing and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry were used to confirm the species identification as P. multocida. Previous reports in the literature are also reviewed.

The human immunodeficiency virus is notorious for its ability to evade the immune system. As well as its ability to escape from cell-mediated and humoral immune responses, new insights are detailing its subversive, pernicious interactions with the innate immune system. The molecular mechanisms underlying these processes highlight potential therapeutic and vaccination strategies.

A 43-year-old previously healthy solicitor presented with a 9-day history of cough productive of yellow sputum with a prodrome of sore throat and myalgia. The cough was paroxysmal in nature and severe enough to cause extensive bilateral subconjunctival haemorrhages and cough syncopes multiple times a day, with one bout of associated haematemesis on the day of admission. He was isolated, treated for a presumed atypical chest infection with tazocin and clarithromycin, and monitored carefully until the hyponatraemia on presentation was resolved. Atypical screen and blood cultures were sent off, though unexciting at first, eventually confirmed the unlikely; Bordetella pertussis, much to the surprise of many who had Legionella as the top differential.