- Volume 2, Issue 2, 2020

Background: Although Cytomegalovirus (CMV) reactivation is not uncommon in critically ill patients, it has not been studied for cirrhotic patients in Liver-ICU.

Methods: CMV reactivation (CMV-plasma-DNAemia; ≥ 500 IU/ml), risk factors and clinical outcomes were assessed among sero-positive non-immunosuppressed critically ill cirrhotic adults at day 0, 7, 14 and 21 in Liver-ICU.

Results: Of 94 consecutive patients in Liver-ICU monitored, 55(48 men) patients were enrolled. Overall, 20 critically ill cirrhotic adults showed CMV reactivation with a median day for follow-up of 11 (IQR: 8 to 18). Majority (n=17/55, 30.9%; CI: 19.1-44.8) showed CMV reactivation at day 7. During 21-day follow-up, incidence rate/density of CMV reactivation was 2.75% per person-day (95% CI: 1.68 - 4.26% per person-day).Total leucocyte count (day 0) was an independent risk factor for CMV reactivation (adjusted OR: 1.15, 95% CI: 1. 00-1. 32, p=0.04) with cut-off point of 19.05 (AUROC: 0.696, 95% CI: 0.547-0.844, p=0.017). Increased nosocomial infection (p=0.009), SIRS (p=0.01) and ARDS (p=0.04) were observed at day 7, coinciding with CMV reactivation during Liver-ICU stay. ICU-Mortality (61.8%) did not significantly differ with and without CMV reactivation. (55 % vs. 65.7%, p= 0.43). Patients with CMV reactivation experienced early death and slightly longer stay in Liver-ICU. (Log rank p=0.06 and 0.17, respectively).

Conclusions: CMV reactivation occurs frequently with leucocytosis being an independent risk factor among critically ill non-immunosuppressed cirrhotic adults. Although CMV reactivation was associated with more severe organ dysfunction during Liver-ICU stay, it did not significantly influence ICU-mortality and Length of Liver-ICU stay.

Introduction

Listeria monocytogenes is a rare cause of infection following endovascular aneurysm repair (EVAR); there remains lack of consensus on the optimal management strategy, in particular the need for life-long suppression. Despite this organism’s increased pathogenicity amongst immunosuppressed hosts, to date no EVAR infections have been described in this cohort.

Here we describe the first case ofListeria monocytogenesEVAR infection in an immunocompromised host.

Case description

A 75-year-old gentleman presented with a 5-day history of back pain, fever and dysuria despite 3 days of oral co-amoxiclav for presumed urinary tract infection. There was no recent gastrointestinal upset. Admission blood and urine cultures were negative.

Past medical history included on-going methotrexate therapy for rheumatoid arthritis and EVAR of the infra-renal aorta in 2013.

A CT abdomen, performed to exclude intra-abdominal pathology, revealed an enlarged aneurysmal sac and fat stranding, secondary to inflammation. A CT-guided sample of aneurysmal fluid was obtained before commencing empirical piperacillin-tazobactam and vancomycin; Listeria monocytogeneswas isolated from subculture after 5 days broth enrichment. The EVAR was removed and replaced 7 days after admission and antimicrobials rationalised to intravenous amoxicillin, ciprofloxacin and metronidazole.

The patient completed 6 weeks intravenous therapy, then commenced lifelong suppressive therapy with oral co-trimoxazole 960mg OD.

Discussion

Listeria monocytogenesEVAR infection has been described in only 8 patients; this is the first in an immunosuppressed patient. This case adds to the literature by outlining a putative management strategy, involving explanation and life-long antimicrobials, for immunocompromised patients with Listeria monocytogenes EVAR infection.

Background: A 33 year old HIV-negative Gambian, who hadn’t left the UK for 7 years, presents with haemoptysis, 6 month cough, sweats, and weight loss. He completed standard treatment for presumed pulmonary TB in Banjul (2006), with a completely normal CXR (2015). He was normotensive, with low grade fever, Hb 110, normal clotting, mild neutropenia, CRP 11, ESR 88, with bilateral cavitating lesions in upper lobes, calcified cavity in the left apex, and tree-on bud appearance throughout left lung, suggestive of active TB. He acutely deteriorated with projectile haemoptysis, leading to haemodynamic compromise requiring tranexamic acid and embolisation of bronchial arteries.

Investigations: IGRA negative. CD4 634 (44%). The ϒ-IFN axis was tested, excluding a complete defect in the IL12-signalling-pathway. Bronchial-alveolar-lavage smear and PCR negative for MTB. Serial induced-sputa however, cultured and identified M.Kansasii, a Non-Tuberculous-Mycobacterium (NTM) on Whole-Genome-Sequencing.

Management: In absence of any radiological structural lung disease, with apparent immune-competence, the source of acquisition remains elusive. Empirical treatment included Ethambutol/Rifampicin/Isoniazid/Moxifloxacin/Clarithromycin and intravenous Amikacin for 6 weeks, to cover for reinfection/relapse with resistant-MTB, as well as NTB. Rifamycin, which is the critical component for treatment success, had to be stopped due to transminitis after 1 month. We rationalised to a multi-drug regime containing ≥3 active agents as an effective course, based on analogy of patients with rifampin-resistance. This led to normalisation of ESR and 2.2kg weight gain, plus radiological resolution 8 months into treatment. He continues to receive a minimum of twelve months after culture-conversion.

Background. Scottish antimicrobial prescribing in the community has fallen since 2012, but this could have unintended consequences. The aim was to examine associations between changes in antibiotic prescribing in primary care and hospital admissions and patient satisfaction.

Methods. Data for 877 Scottish general practices with 5.1 million patients were provided by NHS National Services Scotland. Practices were classified into four equal groups (quartiles) in terms of change in total antibiotic prescribing (rate/1000 registered patients in each quarter) 2012-2018. Changes in hospital admission with infection were examined comparing the four groups. Multivariate regression examined associations between change in antibiotic prescribing and patient satisfaction with the practice using national survey data.

Results. Across Scotland, primary care antibiotic prescribing decreased by 15% from 194.1 (95%CI 193.8-194.4) in Q1 2012 to 165.3 (95%CI 165.0-165.6 ) in Q2 2012, with considerable variation between practices (non-significant increase of 0.22 prescriptions/1000/quarter [p=0.49] for the quartile of practices with least reduction in antibiotic prescribing, vs reduction of -2.95 prescriptions/1000/quarter [p<0.001] for quartile with the largest reduction). Rates of hospital admissions with infection increased over the time period but there were no significant association with changes in antibiotic prescribing. Patient satisfaction decreased over the period, but change in antibiotic prescribing was not associated with patient satisfaction.

Conclusion. There have been clinically significant reductions in Scottish primary care antibiotic use since 2012, varying considerably between practices. Longitudinal analysis of Scotland-wide practice level data found no associations between practice-level reductions in primary care antibiotic prescribing and hospital admissions or patient satisfaction.

Introduction: Dalbavancin is a novel lipoglycopeptide antibiotic which provides gram positive cover including MRSA and enterococci for up to six weeks with two doses. We report the use of Dalbavancin at the Royal Sussex County Hospital in Brighton from 2018-2019.

Methods: Patients were given dalbavancin after approval by a consultant microbiologist on a case by case basis.

Results: 20 patients in total received dalbavancin during this time period. 11 out of 20 patients were male with a mean sample age of 54. 14 patients were ex or current IVDUs. The most frequent dose of dalbavancin given was 1.5g single dose in 11 out of 20 patients.

14 patients had a confirmed bacteraemia. There were 8 cases of MSSA, 1 case of MRSA, 1 CNS, 2 IGAS, 1 Group C Streptococcus and 2 Streptococcus dysgalactiae bacteraemias (one patient had 2 organisms identified in blood cultures). The commonest source of infection was skin and soft tissue, identified in 11 out of 20 patients.

Patients had received a median of 2 (range 1-5) different antibiotics prior to use of dalbavancin with a median course of 14 (range 1 – 27) days Abx prior to Dalbavancin. Patients were admitted for a mean of 15 days with a mean of 12 bed days saved per patient. There was one readmission during this time period which was due to a gram-negative sepsis.

Discussion:Given the challenges of managing severe infections in PWID, dalbavancin can be a “silver bullet” to facilitate effective treatment of important gram-positive pathogens.

Introduction

Pleural empyema is an uncommon but serious condition defined by infected fluid in the pleural space. These patients are often given long courses of empirical broad-spectrum antibiotics as the yield from conventional culture methods is notoriously low. The literature shows that with conventional culture methods of the pleural fluid up to 40-60% of causative pathogens remain unidentified. In recent years methods such as DNA analysis have been developed in an attempt to increase identification rates of pathogens. This paper aims to review the literature to determine the additional benefit of DNA analysis methods above conventional culture of fluid in pleural empyema.

Methods

A review of the literature searching for studies investigating bacteria present in pleural fluid in patients with empyema was carried out. Studies in which adult patients had a diagnosis of empyema and where conventional culture and molecular methods were used to identify the causative bacteria were included. Descriptive statistics were used to compare the increased yield from molecular methods.

A 48yr old man presented with a 1-2 week history of diarrhoea and fever. He took occasional ibuprofen for migraines but took no regular medications and was fit and active. On presentation to A+E blood tests revealed severe AKI with hyperkalaemia, low platelets and anaemia with raised inflammatory markers. He complained of shortness of breath with a CXR consistent with ARDS. He was commenced on IV antibiotics and was transferred to ITU for further management. While on ITU his blood film revealed evidence of haemolysis, in addition to an LDH of >2600. He had persistenly low platelets (14 at its nadir), requiring platelet transfusion. His renal failure was managed with haemofiltration and he was transfused to maintain his Hb above 80. The diagnosis was of haemolytic uraemic syndrome due to a presumed infectious origin. Blood cultures came back positive for a fastidious, slow-growing Gram-negative rod, identified as Capnocytophaga canimorsus. Further questioning revealed the presence of a dog bite to his R. index finger two months previously. The patient's antibiotic regimen was changed to Ceftriaxone 2g IV OD and metronidazole 500mg IV TDS and he was transferred to the Royal Free Hospital to commence haemodilaysis and for specialist renal management.

Capnocytophaga canimorsus is an encapsulated organism known for its potential to cause disseminated and fatal infection in asplenic or immunocompromised patients, which were risk factors not present in our case. It is a rare cause of HUS and highlights the need for thorough history if an infective agent is presumed.

NICE guidelines suggest cases of community acquired pneumonia (CAP) in hospital have blood and sputum cultures and legionella and pneumococcal antigen tests be considered in specific cases. Local guidelines advise respiratory viral swabs, sputum and blood culture in specific cases and urinary antigen tests only in severe cases. We assessed the frequency and appropriateness of microbiological testing in CAP.

Background: Knowledge, attitude, practice and implementation of community pharmacist role in treating tuberculosis patients. Community Pharmacy education in India faces many challenges. An assessment of the challenges and opportunities of community pharmacist role in eradication of Tuberculosis in India has not been conducted.

Methods: This was a cross sectional study A one-day training was conducted in 6th may 2019 in Belagavi , Karnataka state, India. A selected sample of stake holders was invited experts Like Medical education expert in the field of tuberculosis, District Tuberculosis controller officer, Deputy Drugs controller, Assistant Drugs controller. The training Program was conducted by Dept. of Pharmacy Practice, KLE college of Pharmacy, Belagavi in association with District Tuberculosis center Belagavi and Regional office of Deputy Drugs Controller, Belagavi, India.

Results: A total of 60 community pharmacists are responded. The lowest number of correct answers were to the questions were Patients with active TB disease can infect people by talking (56.7%), TB is often spread from person to person through sex (53.3%), aware of Public Private mix (PPM) for Tuberculosis control and care (35%), Anti-TB drugs which are contraindicated in pregnancy (35%).

Conclusion: There are significant gap in knowledge, Attitude and practice on TB infection and control among community pharmacist. Proper training is essential to overcome the gap between community pharmacist and Government sector to eradicate TB by 2025 from India.

Background:Overuse of antibiotics has been linked to the global growth of antimicrobial resistance (AMR). In 2018, increase in meropenem usage in our hospital revealed that we achieved the “Start Smart” but not “Then Focus” element. Following revised carbapenem stewardship, we aimed to evaluate the adherence to guidelines, by monitoring patients initiated on meropenem.

Methods:As part of the antimicrobial stewardship (AMS) at our 1800-bed teaching hospital, carbanepem stewardship was revised in September 2018 and required consultant approval for all carbapenem initiation or continuation following specialist advice. Meropenem prescriptions in adult and paediatric patients were generated from the electronic prescription system and reviewed daily for one week in August 2019 to ascertain if prescribed in line with guideline recommendations or on the advice of microbiology or infectious diseases.

Results:Sixty patients were reviewed. Microbiology or Infectious Diseases recommendation was obtained in 37% of patients. 95% had samples taken where blood cultures accounted for 85% but over a third of these had no growth reported. Meropenem was initiated empirically in 50% of patients mainly for neutropenic sepsis while 28% were culture directed. 35% of patients were escalated from piperacillin-tazobactam of which 57% had neutropenia while de-escalation occurred in 10%.

Conclusion:AMR is related directly to antibiotic use at a patient level. Our revised strategy resulted in a reduction of total carbapenem DDD/1000 Admission from 128 (June 2018) to 87 (June 2019) through improved adherence to guideline and infection specialists recommendations however more work is required to promote switch to narrower-spectrum choice.

BACKGROUND

There has been a national drive to improve antimicrobial stewardship in the diagnosis and management of uncomplicated lower urinary tract infections (UTIs). While much attention has been paid to the initial management in hospital, there is little evidence of how treatment is rationalised or altered in response to results from the laboratory.

METHODS

We undertook a retrospective analysis of medical records, including patients diagnosed with uncomplicated lower UTI whilst in hospital. Data was collected on whether a urine sample was sent to the laboratory, the result was documented, which subsequent actions were taken by clinical teams and their appropriateness.

RESULTS

All the patients received antibiotics for a lower UTI. 55% of patients had documented symptoms of a UTI, the remainder were commenced due to a suspected UTI in the absence of localising clinical symptoms. 86% had an MSU sample sent to the laboratory. In all cases, clinicians had viewed these results. In 57%, the findings of the MSU were documented. 38% of all results were not acted on appropriately, with 19% of those continuing antibiotics unnecessarily, 24% not narrowing down therapy and 12% not changing antibiotics in response to resistant isolates.

CONCLUSION

Whilst correct clinical investigations may be sent and reviewed in the management of uncomplicated UTIs, the results of these are often not documented in the patient’s record and a significant proportion of these results are not acted on appropriately.

Sepsis is defined as life threatening organ dysfunction caused by a dysregulated host response to infection, and is responsible for 52,000 deaths in the UK per year. Approximately 50% of sepsis episodes are related to bacteria where the Gram-negative bacteria Escherichia coli is a leading causative agent. Our previous work with the Hywel Dda Health Board has identified a high level of E. coli sepsis and in the current work, we aim to identify genetic (genes) and host biomarkers (e.g. IL-6) to discriminate E. coli sepsis isolates based on original source of infection.

E. coli isolates (n=100) from blood cultures in patients with defined sources of infection (urinary, biliary, intra-abdominal or unknown) were used to investigate potential biomarkers using next generation sequencing, whole blood modelling and molecular microbiology phenotyping.

Sequencing of isolates is underway. Growth curve analysis demonstrated that human serum could modulate E. coli growth to three phenotype groups; i) no growth, ii) retarded / decreased growth and iii) unaffected growth (compared to LB control). Whole blood modelling over 6 hours confirmed 4 hours to be the optimal time point to study IL-6 expression. Grouping isolates by source of infection showed that those from the urinary tract and ‘unknown’ sources produced significantly more IL-6 than E. coli K12. Completion of phenotyping will allow association studies to bacterial genotype.

These results will help define new biomarkers associated with the host and genetic biomarkers associated with E. coli that will better predict and inform the diagnosis and treatment of sepsis.

Campylobacter jejuniis the world’s most common food-borne pathogen. Campylobacterpathogenesis involves translocation across the intestinal epithelial cell barrier in both humans and chickens and previous work has suggested that strains of E. coli (ExPEC / APEC) may facilitate this process. This study aims to determine the effect that this relationship may have upon the invasive and adhesive potential of the two microbes using our recently published human and avian in vitromodel.

Invasiveness of C. jejuni and E. coli strains were measured using human (Caco-2) and avian (8E-11) epithelial cell lines derived from the gastrointestinal tract and were characterised by epifluorescent and confocal microscopy. Adhesion and invasion assays were carried out to determine the pathogenicity of the different bacteria. Metabolic activity of Caco-2 and 8E-11 together with bacterial strains using alamar blue assay.

Confocal and epifluorescence microscopy determined the strong presence of cytokeratin in Caco-2 cells whilst weak to medium signals were detected in 8E-11 cells. Optimal doses and times for of gentamicin across all strains was 0.02mg/ml for 90 minutes which did not affect metabolic activity of epithelial cells. Significant diversity was found in the adhesive/invasive potential of bacteria when exposed to human and avian cell types. The metabolic rate of C. jejuni (11168) and E. coli (K12) was investigated with the presence of K12 having negative impacts upon the activity of 11168.

The model described here will provide opportunity to improve our understanding of Campylobacterinvasion mechanisms in human and chickens so that improved strategies to negate these consequences may be designed.