Background COVID-19 is infrequently complicated by bacterial co-infection, but antibiotic prescriptions are common. We used community-acquired pneumonia (CAP) as a benchmark to define the processes that occur in bacterial pulmonary infections, testing the hypothesis that baseline inflammatory markers and their response to antibiotic therapy could distinguish bacterial co-infection from COVID-19. Methods Retrospective cohort study of CAP (lobar consolidation on chest radiograph) and COVID-19 (PCR detection of SARS-CoV-2) patients admitted to Royal Free Hospital (RFH) and Barnet Hospital (BH), serving as independent discovery and validation cohorts. All CAP and >90% COVID-19 patients received antibiotics on hospital admission. Results We identified 106 CAP and 619 COVID-19 patients at RFH. Compared with COVID-19, CAP was characterized by elevated baseline white cell count (WCC) [median 12.48 (IQR 8.2–15.3) versus 6.78 (IQR 5.2–9.5) ×106 cells/mL, P < 0.0001], C-reactive protein (CRP) [median 133.5 (IQR 65–221) versus 86.0 (IQR 42–160) mg/L, P < 0.0001], and greater reduction in CRP 48–72 h into admission [median ΔCRP −33 (IQR −112 to +3.5) versus +14 (IQR −15.5 to +70.5) mg/L, P < 0.0001]. These observations were recapitulated in the independent validation cohort at BH (169 CAP and 181 COVID-19 patients). A multivariate logistic regression model incorporating WCC and ΔCRP discriminated CAP from COVID-19 with AUC 0.88 (95% CI 0.83–0.94). Baseline WCC >8.2 × 106 cells/mL or falling CRP identified 94% of CAP cases, and excluded bacterial co-infection in 46% of COVID-19 patients. Conclusions We propose that in COVID-19, absence of both elevated baseline WCC and antibiotic-related decrease in CRP can exclude bacterial co-infection and facilitate antibiotic stewardship efforts.

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Background COVID-19 is infrequently complicated by secondary bacterial infection, but nevertheless antibiotic prescriptions are common. We used community-acquired pneumonia (CAP) as a benchmark to define the processes that occur in a bacterial pulmonary infection, and tested the hypothesis that baseline inflammatory markers and their response to antibiotic therapy could distinguish CAP from COVID-19. Methods In patients admitted to Royal Free Hospital (RFH) and Barnet Hospital (BH) we defined CAP by lobar consolidation on chest radiograph, and COVID-19 by SARS-CoV-2 detection by PCR. Data were derived from routine laboratory investigations. Results On admission all CAP and >90% COVID-19 patients received antibiotics. We identified 106 CAP and 619 COVID-19 patients at RFH. CAP was characterised by elevated white cell count (WCC) and C-reactive protein (CRP) compared to COVID-19 (median WCC 12.48 (IQR 8.2-15.3) vs 6.78 (IQR 5.2-9.5) x106 cells/ml and median CRP CRP 133.5 (IQR 65-221) vs 86 (IQR 42-160) mg/L). Blood samples collected 48-72 hours into admission revealed decreasing CRP in CAP but not COVID-19 (CRP difference -33 (IQR -112 to +3.5) vs +15 (IQR -15 to +70) mg/L respectively). In the independent validation cohort (BH) consisting of 169 CAP and 181 COVID-19 patients, admission WCC >8.2x106 cells/ml or falling CRP during admission identified 95% of CAP cases, and predicted the absence of bacterial co-infection in 45% of COVID-19 patients. Conclusions We propose that in COVID-19 the absence of both elevated baseline WCC and antibiotic-related decrease in CRP can exclude bacterial co-infection and facilitate antibiotic stewardship efforts.

16S ribosomal-ribonucleic acid polymerase chain reaction (PCR) and targeted PCR aid microbiological diagnosis in culture-negative clinical samples. Despite routine clinical use, there remains a paucity of data on their effectiveness across a variety of clinical sample types, and cost-effectiveness. In this 4 year multicentre retrospective observational study, all clinical samples referred for 16S PCR and/or targeted PCR from a laboratory network serving seven London hospitals were identified. Laboratory, clinical, prescribing, and economic variables were analysed. 78/607 samples were 16S PCR positive; pus samples were most frequently positive (29/84; p < 0.0001), and CSF least (8/149; p = 0.003). 210/607 samples had targeted PCR (361 targets requested across 23 organisms) with 43/361 positive; respiratory samples (13/37; p = 0.01) had the highest detection rate. Molecular diagnostics provided a supportive microbiological diagnosis for 21 patients and a new diagnosis for 58. 14/91 patients with prescribing information available and a positive PCR result had antimicrobial de-escalation. For culture-negative samples, mean cost-per-positive 16S PCR result was £568.37 and £292.84 for targeted PCR, equating to £4041.76 and £1506.03 respectively for one prescription change. 16S PCR is more expensive than targeted PCR, with both assisting in microbiological diagnosis but uncommonly enabling antimicrobial change. Rigorous referral pathways for molecular tests may result in significant fiscal savings. Molecular diagnostics have significantly enhanced laboratory ability to detect and identify bacteria in clinical samples 1,2 Whilst bacterial culture is considered the gold standard for microbiological diagnosis, there may be a 24-48 hour delay in providing a result for typical organisms and longer for slow-growing organisms such as Mycobacteria spp 3. Furthermore, false negative culture results may arise from fastidious organisms, non-viable bacteria, or prior use of antimicrobials, potentially affecting patient management. Two methods of Polymerase Chain Reaction (PCR) are recommended as supplementary tests by the United Kingdom Standards of Microbiology Investigations (SMI); targeted PCR and 16S ribosomal ribonucleic acid (rRNA) PCR 4. 16S PCR is a pan-bacterial molecular diagnostic test 5,6 , whilst targeted PCR looks for a finite range of organism targets where specific pathogenic organisms are suspected 7. Identification of causative organisms through targeted PCR or 16S PCR may influence clinical management decisions, serving to support or provide a microbiological diagnosis or impacting antimicrobial prescribing decision-making 8,9. The utility of 16S PCR in identifying causative organisms from specific sterile site samples has been demonstrated in multiple isolated clinical syndromes 10-15. The wider utility of 16S PCR has been evaluated by Rampini et al. 16 , who demonstrated a sensitivity and specificity of 42.9% and 100% for culture-negative bacterial infections respectively. This study did not evaluate the functi...

Background: Since 2015, we prescribed dolutegravir (DTG)-based two drug regimens (DTG-2DR) for 620 people [total cohort 3133 (19.8%)].Method: Clinic database search 1 January 15 to 31 October 21. Demographic, tolerability and HIV related data analysed.Results: In total, 620 people identified; 561 had complete data. 446 male (79.5%); median age 54 years (interquartile range 46, 59). 343 (61.1%) MSM. Nine people who initiated naı ¨vely achieved viral suppression (100%). 546/552 (99.0%) switched or continued and were suppressed at data censor. 460/552 (83.3%) received DTG-lamivudine (DTG/3TC), 74/552 (13.4%) received DTG-rilpivirine (DTG/RPV) and 18/552 (3.3%) received DTG-emtricitabine (DTG/FTC). 70 (12.5%) switched off DTG-2DR (55 DTG/3TC, 13 DTG/RPV, two DTG/FTC) due to side-effects. 41 episodes of blip (1 off >50 copies/ml) occurred in 30 people (5.3%). 11/41 on DTG-RPV [n ¼ 7 multi-tablet regimen (MTR), n ¼ 4 single tablet regimen (STR)]. 27/41 DTG-3TC, 3/41 DTG/FTC (n ¼ 26 MTR, n ¼ 4 STR). Six people (1.1%) failed (confirmed viral load >200 copies/ml or persistent low level viraemia) (n ¼ 4 DTG-3TC STR, n ¼ 1 DTG-3TC MTR, n ¼ 1 DTG-RPV MTR). Four failures due to low level viraemia, one due to non-adherence and one due to high viral load. Resistance tests performed for 5/6 -mutations detected only in latter person with high viral load failure (on DTG-3TC MTR) who developed triple class resistance. Conclusion:Majority of experience is in DTG/3TC stable switch. Minority of patients developed side-effects. Low number of virological failures, one developed integrase inhibitor resistance. Viral failure associated with MTR, commensurate with trial data showing no failure with resistance if DTG/3TC STR used. Overall DTG-2DR demonstrates high efficacy in real-world setting.