Impact of penicillin allergy records on antimicrobial prescribing in hospitalised patients.

BACKGROUND: The overdiagnosis of penicillin allergy and misclassification of non-truly allergic reactions is a growing public health problem, associated with the overuse of broad-spectrum and restricted antimicrobials. We aimed to evaluate the impact of penicillin allergy status on antimicrobial prescribing. METHODS: A retrospective study of inpatients with a documented penicillin allergy receiving antimicrobials was conducted from 1 April to 1 July 2021. Antimicrobial prescribing and clinical characteristics were compared between patients with an active penicillin allergy label and those whose label was removed following antimicrobial stewardship team review. Antimicrobials were classified in two categories: i) 'Access' (recommended), ii) 'Watch and Reserve' (restricted) according to WHO AWaRe classification, a tool to guide appropriate antibiotic use. RESULTS: 437 patients with a documented penicillin allergy receiving antimicrobials were included. 353 patients with an active penicillin allergy label, more frequently received antimicrobials from the 'Watch and Reserve list' (283;80% vs 30;37%; p<0.001). In contrast, 84 patients who were de-labelled received more often antimicrobials from the 'Access list' (53;63% vs 64;18%; p<0.001). CONCLUSIONS: Penicillin allergy reviews and de-labelling strategies may reduce the use of restricted antimicrobials under the 'Watch and Reserve list'. This practice should be encouraged and reinforced in all hospitals.

Improving anaemia diagnosis using peripheral blood smear with remote interpretation in adults living with HIV with moderate to severe anaemia: A prospective study nested within the Kilombero and Ulanga antiretroviral cohort.

INTRODUCTION: In low-resource settings, anaemia is a very common condition. Identification of anaemia aetiologies remains challenging due to the lack of diagnostic tools and expertise. We aimed to improve anaemia diagnostics using peripheral blood smear (PBS) with remote interpretation in people living with HIV (PLHIV) with moderate to severe anaemia. METHODS: We conducted a prospective study nested within the Kilombero and Ulanga Antiretroviral Cohort, including non-pregnant PLHIV aged ≥18 years presenting with moderate (haemoglobin 7.0-9.9 g/dl) or severe (<7.0 g/dl) anaemia at any visit from January 2019 to December 2020. For each participant, ten PBS images, full blood count and clinical details were shared with a haematologist for remote interpretation (enhanced care). Identification of anaemia etiologies and potential impact on treatment was compared between enhanced and standard care. RESULTS: Among 400 PLHIV with moderate to severe anaemia, 349 (87%) were female, median age was 40 years (interquartile range (IQR) 35-46)), 65 (17%) had a body mass index <18.5 kg/m2, 215 (54%) had HIV WHO stage III/IV, 79 (20%) had a CD4 cell count <200 cells/µl and 317 (89%) had HIV viral load <100 copies/ml. Severe anaemia was diagnosed in 84 (21%). Suspected multiple aetiologies were documented more frequently by enhanced care compared to standard care 267 (67%) vs 20 (5%); p<0.001. Suspected iron deficiency was the most frequent aetiology (n = 337; 84%), followed by chronic disease (n = 199; 50%), folate/vitamin B12 deficiency (n = 78; 20%) and haemoglobinopathy (n = 83; 21%). In 272 participants (68%), enhanced care revealed additional clinically relevant findings with impact on the treatment recommendation. CONCLUSION: Remote interpretation of PBS combined with clinical information and blood cell count results can provide insights to the suspected aetiological diagnosis of moderate and severe anaemia in rural low-resource settings and impact specific treatment.

National action plans for antimicrobial resistance and variations in surveillance data platforms.

Objective: To assess how national antimicrobial susceptibility data used to inform national action plans vary across surveillance platforms. Methods: We identified available open-access, supranational, interactive surveillance platforms and cross-checked their data in accordance with the World Health Organization's (WHO's) Data Quality Assurance: module 1. We compared platform usability and completeness of time-matched data on the antimicrobial susceptibilities of four blood isolate species: Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Streptococcus pneumoniae from WHO's Global Antimicrobial Resistance and Use Surveillance System, European Centre for Disease Control's (ECDC's) network and Pfizer's Antimicrobial Testing Leadership and Surveillance database. Using Bland-Altman analysis, paired t-tests, and Wilcoxon signed-rank tests, we assessed susceptibility data and number of isolate concordances between platforms. Findings: Of 71 countries actively submitting data to WHO, 28 also submit to Pfizer's database; 19 to ECDC; and 16 to all three platforms. Limits of agreement between WHO's and Pfizer's platforms for organism-country susceptibility data ranged from -26% to 35%. While mean susceptibilities of WHO's and ECDC's platforms did not differ (bias: 0%, 95% confidence interval: -2 to 2), concordance between organism-country susceptibility was low (limits of agreement -18% to 18%). Significant differences exist in isolate numbers reported between WHO-Pfizer (mean of difference: 674, P-value: < 0.001, and WHO-ECDC (mean of difference: 192, P-value: 0.04) platforms. Conclusion: The considerable heterogeneity of nationally submitted data to commonly used antimicrobial resistance surveillance platforms compromises their validity, thus undermining local and global antimicrobial resistance strategies. Hence, we need to understand and address surveillance platform variability and its underlying mechanisms.

Clinical, microbiological characteristics and predictors of mortality in patients with carbapenemase-producing Enterobacterales bloodstream infections: a multicentre study.

Objectives: To investigate the clinical, microbiological characteristics and outcomes of patients with bloodstream infections (BSI) due to carbapenemase-producing Enterobacterales (CPE). Methods: A multicentre retrospective observational study of patients with BSIs due to CPE admitted to six UK hospitals was conducted between 2011 and 2021. Multivariate analysis was used to identify factors predicting 30-day case fatality rate (CFR). Results: There were 84 episodes of CPE-BSIs, 37 (44%) due to OXA-48, 35 (42%) to metallo-betalactamases (MBL) and 12 (14%) to KPC. 63% of patients were male with a median age of 64 years. Common organisms included Klebsiella spp. (61%), Escherichia coli (20%) and Enterobacter spp. (13%). Urinary devices were more often involved in OXA-48 BSIs (12/37; 32%) compared to infections caused by MBL and KPC (4/35; 11% and 1/12; 8%; P = 0.046). In contrast, central venous catheters were more frequently present in KPC-BSIs (10/12; 92%) compared with OXA-48 and MBL (11/37; 30% and 20/35; 57%; P = 0.002). Effective definitive antimicrobials were received by 72/84 (86%) patients, comprising monotherapy (32/72; 44%) or combination therapy (40/72; 56%). 30-day case fatality rate (CFR) was 38%. Sepsis or septic shock was associated with death [OR 3.81 (CI 1.19-12.14), P = 0.024]. Conclusion: Strategies targeting high-risk patients and adherence to infection prevention bundles for urinary devices and central venous catheters can reduce OXA-48 and KPC-BSIs. Early recognition and management of severe sepsis, prompt initiation of appropriate antimicrobial therapy and development of novel antimicrobials are crucial to mitigate the high CFR associated with CPE-BSIs.

An analysis of existing national action plans for antimicrobial resistance-gaps and opportunities in strategies optimising antibiotic use in human populations.

At the 2015 World Health Assembly, UN member states adopted a resolution that committed to the development of national action plans (NAPs) for antimicrobial resistance (AMR). The political determination to commit to NAPs and the availability of robust governance structures to assure sustainable translation of the identified NAP objectives from policy to practice remain major barriers to progress. Inter-country variability in economic and political resilience and resource constraints could be fundamental barriers to progressing AMR NAPs. Although there have been regional and global analyses of NAPs from a One Health and policy perspective, a global assessment of the NAP objectives targeting antimicrobial use in human populations is needed. In this Health Policy, we report a systematic evidence synthesis of existing NAPs that are aimed at tackling AMR in human populations. We find marked gaps and variability in maturity of NAP development and operationalisation across the domains of: (1) policy and strategic planning; (2) medicines management and prescribing systems; (3) technology for optimised antimicrobial prescribing; (4) context, culture, and behaviours; (5) operational delivery and monitoring; and (6) patient and public engagement and involvement. The gaps identified in these domains highlight opportunities to facilitate sustainable delivery and operationalisation of NAPs. The findings from this analysis can be used at country, regional, and global levels to identify AMR-related priorities that are relevant to infrastructure needs and contexts.

16S rDNA PCR for the aetiological diagnosis of culture-negative infective endocarditis.

INTRODUCTION: Culture-negative infective endocarditis (IE) accounts for 7-31% of all cases. Metagenomics has contributed to improving the aetiological diagnosis of IE patients undergoing valve surgery. We assessed the impact of 16S ribosomal DNA gene polymerase chain reaction (16S rDNA PCR) in the aetiological diagnosis of culture-negative IE. METHODS: Between January 2016 and January 2020, clinical data from culture-negative IE patients were reviewed retrospectively. Identification of bacteria was performed using 16S rDNA PCR in heart valve specimens. RESULTS: 36 out of 313 patients (12%) with culture-negative IE had their valve tissue specimens submitted for 16S rDNA PCR. 16S rDNA PCR detected and identified bacterial nucleic acid in heart valve tissue significantly more frequently compared to valve culture alone 25(70%) vs 5(12%); p < 0.05. Mean age was 57 years (SD 18) and 80% were male. Native and aortic valve were involved in 76% and 52% of cases, respectively. Streptococcus spp. (n 15) were the most commonly detected organisms, followed by bacteria of the HACEK group (Haemophilus parainfluenzae 2, Aggregatibacter actinomycetemcomitans 1), nutritionally variant streptococci (Abiotrophia defectiva 2), and one each of Staphylococcus aureus, Corynebacterium pseudodiphtheriticum, Helcococcus kunzii, Neisseria gonorrhoeae, Tropheryma whipplei. CONCLUSION: 16S rDNA PCR may be a useful diagnostic tool for the identification of the causative organism in culture-negative IE. Efforts towards a shorter turnaround time for results should be consider and further studies assessing the clinical impact of this technique in culture-negative IE are needed.

Diagnostic value of 18F-FDG PET/CT in infective endocarditis.

INTRODUCTION: 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET/CT) is not routinely recommended for the diagnosis of infective endocarditis (IE) due to the lack of clinical impact. MATERIALS AND METHODS: Between January 2016 and January 2020, clinical data from patients with a possible diagnosis of IE were reviewed retrospectively to evaluate the value of 18F-FDG-PET/CT in the diagnosis of IE. 18F-FDG PET/CT scan was performed as an additional diagnostic tool in possible IE when echocardiography was inconclusive or in patients with definite IE to identify extracardiac complications. Cases were classified according to modified Duke criteria as rejected, definite or possible. RESULTS: 313 patients with suspected IE were included. 72 (23%) patients underwent 18F-FDG PET/CT. 18F-FDG PET/CT resulted in a reclassification of Duke criteria in 29/72 (40%) patients, from "possible" to "definite" (n, 10) and to "rejected" (n, 19). Patients who benefited from a Duke criteria reclassification following 18F-FDG PET/CT were more frequently classified as possible IE at inclusion or had a non-conclusive baseline echocardiography (100% vs 58%; p 0.001) and had more likely a prosthetic metallic valve replacement (59% vs 21%; p 0.001). Abnormal perivalvular uptake was identified in 46 patients (71% prosthetic vs 50% native; p 0.118). 18F-FDG PET/CT identified extracardiac uptake consistent with septic emboli in 14/72 (19%) patients. In addition, extracardiac uptake indicative of an alternative diagnosis was identified in 5 patients (2% prosthetic vs 17% native; p 0.039). CONCLUSION: The use of 18F-FDG-PET/CT has shown to be useful in the diagnosis of IE, particularly in prosthetic IE and may provide additional value in the detection of septic emboli and/or the identification of an alternative diagnosis different from IE.

Impact of rapid susceptibility testing on antimicrobial therapy and clinical outcomes in Gram-negative bloodstream infections.

BACKGROUND: Rapid antimicrobial susceptibility testing (rAST) has the potential to improve care of bloodstream infections. OBJECTIVES: The aim of this service evaluation was to assess the impact of rAST on antimicrobial therapy and clinical outcomes in patients with Gram-negative bloodstream infection. METHODS: A prospective service evaluation was conducted from March 2018 to December 2018. A rAST system (Alfred 60AST) was run Monday-Friday before midday and results were communicated to clinicians on the same day as positive blood culture, with subsequent conventional AST performed. Times to antibiotic therapy and clinical outcomes were compared between rAST and conventional AST. RESULTS: One hundred and ninety-one patients with Gram-negative bacteraemia were included (93 in the rapid group and 98 in the conventional group). Aminoglycoside combination therapy was stopped earlier in the rapid group [32 h (0-795) versus 54 h (4-216), P = 0.002]. The median time to optimal antibiotic based on AST results was significantly shorter than that in the conventional group [50 h (10-339) versus 69.5 h (20-872), P = 0.034]. In the subgroup of patients on ineffective empirical antibiotic, time to effective antibiotic was shorter in the rapid group [39.5 h (32-97) versus 57 h (49-83), P = 0.036]. No differences were found in 28 day mortality or length of stay. CONCLUSIONS: Rapid susceptibility testing resulted in faster discontinuation of aminoglycosides and a shorter time to starting effective and optimal antibiotic when compared with conventional AST results. rAST has potential clinical benefits and points to the need for larger future studies in areas of high antibiotic resistance.

Rapid versus standard antimicrobial susceptibility testing to guide treatment of bloodstream infection.

BACKGROUND: Rapid antimicrobial susceptibility tests are expected to reduce the time to clinically important results of a blood culture. This might enable clinicians to better target therapy to a person's needs, and thereby, improve health outcomes (mortality, length of hospital stay), and reduce unnecessary prescribing of broad-spectrum antibiotics; thereby reducing antimicrobial resistance rates. OBJECTIVES: To assess the effects of rapid susceptibility testing versus standard susceptibility testing for bloodstream infections (BSIs). SEARCH METHODS: To identify studies with selected outcomes, we searched the Cochrane Infectious Diseases Group Specialised Register, CENTRAL, MEDLINE, LILACS, and two trials registries, between 1987 and October 2020. We used 'bloodstream infection' and 'antimicrobial susceptibility tests' as search terms. We had no language or publication status limitations. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing rapid antimicrobial susceptibility testing (with a time-to-result of ≤ 8 hours) versus conventional antimicrobial susceptibility testing in people with a BSI caused by any bacteria, as identified by a positive blood culture. DATA COLLECTION AND ANALYSIS: Two review authors independently screened references, full-text reports of potentially relevant studies, extracted data from the studies, and assessed risk of bias. Any disagreement was discussed and resolved with a third review author. For mortality, a dichotomous outcome, we extracted the number of events in each arm, and presented a risk ratio (RR) with 95% confidence interval (CI) to compare rapid susceptibility testing to conventional methods. We used Review Manager 5.4 to meta-analyse the data. For other outcomes, which are time-to-event outcomes (time-to-discharge from hospital, time-to-first appropriate antibiotic change), we conducted qualitative narrative synthesis, due to heterogeneity of outcome measures.  MAIN RESULTS: We included six trials, with 1638 participants. For rapid antimicrobial susceptibility testing compared to conventional methods, there was little or no difference in mortality between groups (RR 1.10, 95% CI 0.82 to 1.46; 6 RCTs, 1638 participants; low-certainty evidence). In subgroup analysis, for rapid genotypic or molecular antimicrobial susceptibility testing compared to conventional methods, there was little or no difference in mortality between groups (RR 1.02, 95% CI 0.69 to 1.49; 4 RCTs, 1074 participants; low-certainty evidence). For phenotypic rapid susceptibility testing compared to conventional methods, there was little or no difference in mortality between groups  (RR 1.37, 95% CI 0.80 to 2.35; 2 RCTs, 564 participants; low-certainty evidence). In qualitative analysis, rapid susceptibility testing may make little or no difference in time-to-discharge (4 RCTs, 1165 participants; low-certainty evidence). In qualitative analysis, rapid genotypic susceptibility testing compared to conventional testing may make little or no difference in time-to-appropriate antibiotic (3 RCTs, 929 participants; low-certainty evidence). In subgroup analysis, rapid phenotypic susceptibility testing compared to conventional testing may improve time-to-appropriate antibiotic (RR -17.29, CI -45.05 to 10.47; 2 RCTs, 564 participants; low-certainty evidence).  AUTHORS' CONCLUSIONS: The theoretical benefits of rapid susceptibility testing have not been demonstrated to directly improve mortality, time-to-discharge, or time-to-appropriate antibiotic in these randomized studies. Future large prospective studies should be designed to focus on the most clinically meaningful outcomes, and aim to optimize blood culture pathways.

COVID-19 cardiac injury and the use of colchicine.

We report a case of cardiac injury in a 46-year-old man affected by COVID-19. The patient presented with shortness of breath and fever. ECG revealed sinus tachycardia with ventricular extrasystoles and T-wave inversion in anterior leads. Troponin T and N-terminal pro B-type natriuretic peptide were elevated. Transthoracic echocardiography showed severely reduced systolic function with an estimated left ventricle ejection fraction of 30%. A nasopharingeal swab was positive for SARS-CoV-2. On day 6, 11 days after onset of symptoms, the patient deteriorated clinically with new chest pain and type 1 respiratory failure. Treatment with colchicine 0.5 mg 8-hourly resulted in rapid clinical resolution. This case report highlights how cardiac injury can dominate the clinical picture in COVID-19 infection. The role of colchicine therapy should be further studied to determine its usefulness in reducing myocardial and possibly lung parenchymal inflammatory responses.

Images of the month: Cavernous sinus venous thrombosis secondary to Streptococcus milleri maxillary sinusitis: An unusual cause of diplopia and headache.

Cavernous sinus venous thrombosis is an uncommon condition associated with high mortality rates if not recognised early. Symptoms include headache, visual loss, ophthalmoplegia, altered consciousness, proptosis and periorbital oedema. High-quality imaging is critical in early diagnosis and successful management. Primary infection (such as sinusitis) and possible complications (including meningitis) should be considered as potential aetiologies of cavernous sinus venous thrombosis, especially in those with a preceding history of localised infection. We present a case of a 50-year-old man with a bilateral cavernous sinus venous thrombosis with associated meningitis caused by Streptococcus milleri, secondary to maxillary sinusitis and otomastoiditis. He was successfully treated with antimicrobial treatment, surgical drainage and anticoagulation.