Objectives: To investigate the incidence of bacterial and fungal coinfection of hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in this retrospective observational study across two London hospitals during the first UK wave of coronavirus disease 2019 . Methods: A retrospective case series of hospitalized patients with confirmed SARS-CoV-2 by PCR was analysed across two acute NHS hospitals (20 Februarye20 April 2020; each isolate reviewed independently in parallel). This was contrasted to a control group of influenza-positive patients admitted during the 2019e2020 flu season. Patient demographics, microbiology and clinical outcomes were analysed. Results: A total of 836 patients with confirmed SARS-CoV-2 were included; 27 (3.2%) of 836 had early confirmed bacterial isolates identified (0e5 days after admission), rising to 51 (6.1%) of 836 throughout admission. Blood cultures, respiratory samples, pneumococcal or Legionella urinary antigens and respiratory viral PCR panels were obtained from 643 (77%), 110 (13%), 249 (30%), 246 (29%) and 250 (30%) COVID-19 patients, respectively. A positive blood culture was identified in 60 patients (7.1%), of which 39 were classified as contaminants. Bacteraemia resulting from respiratory infection was confirmed in two cases (one each community-acquired Klebsiella pneumoniae and ventilator-associated Enterobacter cloacae). Line-related bacteraemia was identified in six patients (three Candida, two Enterococcus spp. and one Pseudomonas aeruginosa). All other community-acquired bacteraemias (n ¼ 16) were attributed to nonrespiratory infection. Zero concomitant pneumococcal, Legionella or influenza infection was detected. A low yield of positive respiratory cultures was identified; Staphylococcus aureus was the most common respiratory pathogen isolated in community-acquired coinfection (4/24; 16.7%), with pseudomonas and yeast identified in late-onset infection. Invasive fungal infections (n ¼ 3) were attributed to line-related infections. Comparable rates of positive coinfection were identified in the control group of confirmed influenza infection; clinically relevant bacteraemias (2/141; 1.4%), respiratory cultures (10/38; 26.3%) and pneumococcal-positive antigens (1/19; 5.3%) were low. Conclusions: We found a low frequency of bacterial coinfection in early COVID-19 hospital presentation, and no evidence of concomitant fungal infection, at least in the early phase of COVID-19.

Background European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint criteria for methicillin-susceptible Staphylococcus aureus (MSSA) treatment with ceftriaxone are based upon high dose (4 g/day) rather than standard dose (2 g/day) posology. This is particularly relevant for invasive infections, and for patients managed via Outpatient Parenteral Antimicrobial Therapy (OPAT), but may result in increased drug toxicity. We quantified the incidence of neutropenia, thrombocytopenia and raised liver enzymes between standard and high dose ceftriaxone in adult patients. Method Adult outpatients prescribed ≥ 7 days of ceftriaxone therapy were identified, and clinical, pharmacological, and laboratory parameters extracted from electronic health records between May 2021 and December 2021. Incidence and median time to haematological and hepto-toxicity were analysed. Univariate odds ratios were calculated for neutrophil count and ALT levels with 95% confidence level and Chi squared/Fisher’s exact test used to identify statistical significance. Results Incidence of neutropenia was comparable between both groups; 8/47 (17%) in the 2 g group vs 6/39 (15.4%) in the 4 g group (OR 0.89 (95% CI 0.26–2.63), p > 0.999). Median time to neutropenia was 12 and 17 days in the 2 g and 4 g groups respectively. Thrombocytopenia was observed in 0/47 in the 2 g group compared with 3/39 (7.7%) in the 4 g group (p 0.089). Median time to thrombocytopenia was 7 days in the 4 g group. Elevated liver enzymes did not clearly correlate with ceftriaxone dosing; present in 5/47 (10.6%) and 2/39 (5.1%) for 2 g and 4 g respectively (OR 0.45 (95% CI 0.87–2.36), p 0.448). Treatment cessation due to any adverse effect was similar between both groups 2/47 (4.3%) for 2 g and 3/39 (7.7%) for 4 g (OR 1.86 (95% CI 0.36–10.92), p 0.655). Conclusions Increased adverse effects with 4 g (over 2 g) daily dosing of ceftriaxone was not observed in an OPAT population. However absolute development of haematological and liver dyscrasias was appreciable—monitoring of liver function and full blood count in patients receiving prolonged ceftriaxone is indicated irrespective of dosing.

Introduction The glycopeptide teicoplanin is commonly utilized to facilitate outpatient parenteral antimicrobial therapy (OPAT). Licensed for once daily maintenance dosing, teicoplanin’s long half-life allows for less frequent dosing (e.g. thrice weekly) following successful loading. This service evaluation reviews the safety and effectiveness of a novel thrice weekly teicoplanin dosing regimen. Methods A retrospective, observational study was conducted at Chelsea and Westminster Hospital (March 2018 to July 2020), evaluating trough serum teicoplanin concentrations for patients receiving >5 days of teicoplanin in the OPAT setting. Teicoplanin dosing and administration (once daily versus thrice weekly), clinical outcomes and therapeutic levels were analysed for all patients. The project was registered with clinical governance locally. Results A total of 82 patients treated with teicoplanin in the OPAT service were included; 53/82 receiving thrice weekly and 29/82 receiving once daily dosing. Mean teicoplanin trough levels were similar in both groups (26.2 mg/L and 25.8 mg/L in once daily and thrice weekly groups, P = 0.8895). High clinical success rates were recorded in both groups (25/29 [86.2%] versus 50/53 [94.3%]). No correlation with clinical outcomes and initial teicoplanin serum levels was identified. Normal renal function (>90 mL/min) was associated with lower teicoplanin serum concentrations (mean [±SD] 21.4 mg/L [±10.1] versus 29.7 mg/L [±14], P = 0.0178) in the thrice weekly dosed group but not with the once daily dosed group (mean [±SD] 28.2 mg/L [±9.4] versus 23.7 mg/L [±9.9], P = 0.2201). Conclusions This study supports thrice weekly teicoplanin as a convenient and effective OPAT for administration in the OPAT setting. Therapeutic drug monitoring is advised to adjust for intra-patient variability.

BackgroundUpdated European Committee on Antimicrobial Susceptibility Testing (EUCAST) amikacin breakpoints for Enterobacterales and Pseudomonas aeruginosa included revised dosing recommendations of 25–30 mg/kg to achieve key pharmacokinetic/pharmacodynamic parameters, higher than recommended in the British National Formulary. The objectives of this review were to identify clinical evidence for high-dose amikacin regimens and to determine drug exposures that are related to adverse events and toxicity.MethodsThe literature search was conducted in October 2021 and updated in May 2022 using electronic databases for any study reporting adult participants treated with amikacin at doses ≥20 mg/kg/day. Reference lists of included papers were also screened for potential papers. Data were extracted for pharmacokinetic parameters and clinical outcomes, presented in a summary table and consolidated narratively. Meta-analysis was not possible. Each study was assessed for bias before, during and after the intervention using the ROBINS-I tool.ResultsNine studies (total 501 participants in 10 reports) were identified and included, eight of which were observational studies. Assessment of bias showed substantial flaws. Dosing regimens ranged from 25 to 30 mg/kg/day. Six studies adjusted the dose in obesity when participants had a body mass index of ≥30 kg/m2. Target peak serum concentrations ranged from 60 mg/L to 80 mg/L and 59.6–81.8% of patients achieved these targets, but there was no information on clinical outcomes. Two studies reported the impact of high-dose amikacin on renal function. No studies reporting auditory or vestibular toxicity were identified.ConclusionAll included papers were limited by a significant risk of bias, while methodological and reporting heterogeneity made drawing conclusions challenging. Lack of information on the impact on renal function or ototoxicity means high-dose regimens should be used cautiously in older people. There is a need for a consensus guideline for high-dose amikacin to be written.Trial registration numberPROSPERO (CRD42021250022).

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Background Amikacin is an aminoglycoside with activity against Gram negative pathogens. Updated EUCAST amikacin breakpoints for Enterobacterales and Pseudomonas aeruginosa included revised dosing recommendations of 25-30mg/kg to achieve key pharmacokinetic/pharmacodynamic parameters, higher than recommended in the British National Formulary. We undertook a literature review to report preferred dosing regimens, monitoring and toxicities associated with the use of amikacin at doses ≥20mg/kg/day. Methods This literature search was conducted in electronic databases for any study reporting adult participants treated with amikacin at doses ≥20mg/kg/day. Data were extracted for pharmacokinetic parameters and clinical outcomes, while papers were assessed for bias using the ROBINS-I tool. Results Nine papers were identified and included, eight of which were observational studies; assessment of bias showed substantial flaws. Dosing regimens ranged from 25-30mg/kg/day. Six studies adjusted the dose in obesity when participants BMI ≥30 kg/m2. Target peak serum concentrations ranged from 60mg/L-80mg/L and 59.6-81.8% of patients achieved these targets. Two studies reported the impact of high dose amikacin on renal function. No studies reporting auditory or vestibular toxicity were identified. Conclusions Dosing amikacin at 25-30mg/kg achieved peak concentration targets in the majority of patients, but there was no information on clinical outcomes. There is little information about the impact on renal function or ototoxicity; caution with use of high dose regimens in older patients for prolonged periods is recommended. Given the paucity of information, there is a need for a consensus guideline for high dose amikacin or a prospective study.

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Background Over-diagnosis of infective aspiration pneumonia is common in healthcare settings and represents a potential for misuse of antimicrobial therapy. Methods A retrospective analysis was undertaken of all hospitalized patients treated for aspiration pneumonia within a multicentre Acute NHS Trust (April–May 2021, London, UK). Data collected included: age, initial antibiotics prescribed, duration of therapy, relevant microbiology (sputum samples or blood cultures) and chest X-ray. Treatment response was analysed including body temperature after 24 h of antimicrobials, use of oxygen support after 48 h, any escalation of antimicrobial therapy and 30 day in-hospital mortality. The study was registered as service evaluation project. Results In total, 94 patients treated for aspiration pneumonia were included; median age 82 years (IQR 67–89). Co-amoxiclav monotherapy was the most frequently prescribed treatment (67/94); cephalosporins (8/94) and ciprofloxacin (4/94) were also commonly used. Duration (median) of treatment was 4.4 days (IQR 1–6.7); 32/94 patients received <48 h. Radiological evidence of consolidation, O2 support at 48 h and fever at 24 h was present in 32/94, 25/94 and 12/94 patients, respectively. A microbiological diagnosis to confirm infection was present in 12/94. Consolidation [OR 2.36 (95% CI 1.04–10.25); P = 0.037] and O2 support at 48 h [OR 3.22 (95% CI 1.02–10.25); P = 0.044], but not fever at 24 h [OR 0.94 (95% CI 0.18–4.80)], were associated with treatment escalation. No association between O2 support/fever and total duration was evident. The 30 day in-hospital mortality was 17% (16/94). Conclusions Aspiration pneumonia has high in-hospital mortality and often necessitates antibacterial treatment. The true incidence of bacterial pneumonia is unclear, and many patients may benefit from early cessation of antibacterial treatment.