Evaluation of the stability of ceftazidime/avibactam in elastomeric infusion devices used for outpatient parenteral antimicrobial therapy utilizing a national stability protocol framework.

Objectives: To evaluate the stability of ceftazidime/avibactam in elastomeric infusers, utilizing the UK's Yellow Cover Document (YCD) stability testing framework, in conditions representative of OPAT practice. Methods: Ceftazidime/avibactam was reconstituted with sodium chloride 0.9% (w/v) in two elastomeric infusers at concentrations (dose) levels of 1500/375, 3000/750 and 6000 mg/1500 mg in 240 mL. The infusers were exposed to a fridge storage (2°C-8°C) for 14 days followed by 24 h in-use temperature (32°C). Results: After 14 days of fridge storage and subsequent 24 h exposure to 32°C, mean ±â€ŠSD of ceftazidime percent remaining was 75.5% ±â€Š1.8%, 79.9% ±â€Š1.1%, 82.4% ±â€Š0.6%, for Easypump, and 81.7% ±â€Š1.2%, 82.5% ±â€Š0.5%, 85.4% ±â€Š1.1% for Dosi-Fuser devices at the high, intermediate and low doses tested, respectively. For avibactam, mean ±â€ŠSD percent remaining was 83.2% ±â€Š1.8%, 87.4% ±â€Š2.0%, 93.1% ±â€Š0.9% for Easypump, and 85.1% ±â€Š2.0%, 86.7% ±â€Š0.1%, 92.5% ±â€Š0.1% for Dosi-Fuser devices. The cumulative amount of pyridine generated in the devices ranged from 10.4 mg at low dose to 76.9 mg at high dose. Regression-based simulation showed that the degradation of both ceftazidime and avibactam was <10% for at least 12 h of the running phase, if stored in a fridge for not more than 72 h prior to in-use temperature exposure. Conclusions: Whilst not meeting the strict UK YCD criteria for ≤5% degradation, ceftazidime/avibactam may be acceptable to administer as a continuous 12 hourly infusion in those territories where degradation of ≤10% is deemed acceptable.

Evaluation of the stability of aciclovir in elastomeric infusion devices used for outpatient parenteral antimicrobial therapy.

OBJECTIVES: To investigate the stability of aciclovir solutions in elastomeric devices used for outpatient parenteral antimicrobial therapy (OPAT). METHODS: Triplicates of two elastomeric devices, Accufuser and Easypump II, were filled with a solution of 200 mg, 2400 mg, and 4500 mg aciclovir in 240 mL 0.9% w/v saline. Devices were stored at room temperature for 14 days, followed by 24 hours storage at 32°C. Assessment using a stability indicating assay, pH and subvisible particle analysis was undertaken at 11 time points throughout the study. RESULTS: Aciclovir solution at 200 mg and 2400 mg in 240 mL was stable for 14 days at room temperature (<20°C) and 24 hours of 32°C 'in-use' temperature exposure, remaining above the 95% limit for NHS stability protocols. The high dose was also stable for 14 days at room temperature, but when stored at 32°C there was precipitation of aciclovir within 4 hours in both devices. The precipitate was confirmed as aciclovir and precipitation was not a sign of chemical degradation. CONCLUSIONS: Aciclovir concentrations above 2400 mg/240 mL are liable to precipitation and cannot be recommended for OPAT services because of heightened risks of nephrotoxicity. Aciclovir solution can be given as a continuous 24-hour infusion for OPAT services at a concentration range of 200-2400 mg in 240 mL in Accufuser and Easypump II elastomeric devices following 14 days storage at room temperature, protected from light.

Selling antibiotics without prescriptions among community pharmacies and drug outlets: a simulated client study from Ghana.

BACKGROUND: Selling antibiotics without prescriptions is mostly illegal worldwide, including in Ghana, and promotes antimicrobial resistance. We evaluated the prevalence and practice of selling antibiotics without prescriptions among community pharmacies (CPs) and drug outlets, for the first time, in Ghana to quantify and characterize this issue to inform future interventions. RESEARCH DESIGN AND METHODS: Two scenarios utilizing the Simulated Client Methodology were enacted: an upper respiratory tract infection of viral origin (scenario one); and pediatric diarrhea (scenario two). CPs/Outlets were selected by stratified proportional random sampling from four metropolitan cities (~14% of the total Ghanaian population). Selling of antibiotics was assessed at three demand levels and its overall prevalence was estimated, then stratified by the study variables. RESULTS: Out of the 265 sampled CPs/outlets, the prevalence of selling antibiotic without prescription was 88.3% (n = 234/265), with variations not only across the four regions [92.5% (n = 123/133) in Kumasi, 87.5% (n = 14/16) in Cape Coast, 84.1% (n = 69/82) in Accra, and 82.4% (n = 28/34) in Tamale] but also across CPs [90% (n = 121/134)] and drug outlets [86% (n = 113/131)]. CONCLUSIONS: A very high prevalence/sub-optimal practice of selling antibiotics without prescriptions was found. This highlights the need to increase compliance with antibiotic dispensing legislation through evidence-based interventions including education of key stakeholders.

Evaluation of duration of antibiotic therapy across hospitals in Scotland including the impact of COVID-19 pandemic: a segmented interrupted time series analysis.

BACKGROUND: Little is known about the duration of antibiotic use in hospital settings. We evaluated the duration of hospital antibiotic therapy for four commonly prescribed antibiotics (amoxicillin, co-amoxiclav, doxycycline, and flucloxacillin) including the assessment of COVID-19 impact. METHODS: A repeated, cross-sectional study using the Hospital Electronic Prescribing and Medicines Administration system (January/2019-March/2022). Monthly median duration of therapy/duration categories was calculated, stratified by routes of administration, age, and sex. The impact of COVID-19 was assessed using segmented time-series analysis. RESULTS: There were significant variations in the median duration of therapy across routes of administration (P < 0.05), with the highest value among those antibiotic courses composed of both oral and IV antibiotics ('Both' group). Significantly higher proportions of prescriptions within the 'Both' group had a duration of >7 days compared to oral or IV. The duration of therapy differed significantly by age. Some small statistically significant changes in the level/trends of duration of therapy were observed in the post-COVID-19 period. CONCLUSIONS: No evidence for prolonged duration of therapy were observed, even during COVID-19 pandemic. The duration of IV therapy was relatively short, suggesting timely clinical review and consideration of IV to oral switch. Longer duration of therapy was observed among older patients.

Evaluation of the stability of temocillin in elastomeric infusion devices used for outpatient parenteral antimicrobial therapy in accordance with the requirements of the UK NHS Yellow Cover Document.

OBJECTIVE: To evaluate the stability of temocillin solution in two elastomeric infusion devices - Easypump II LT 270-27- S and Dosi-Fusor L25915-250D1 for OPAT administration during 14 days of 5°C±3°C fridge storage followed by 24 hour exposure at an in-use temperature of 32°C, when reconstituted with 0.3% citrate buffer at pH7. METHODS: Stability testing was conducted in accordance with standard protocols in the UK National Health Service Yellow Cover Document (YCD). A stability indicating assay method was applied using a high-performance liquid chromatography (HPLC) system with a photodiode array detector. Low (500 mg/240 mL), intermediate (4000 mg/240 mL) and high (6000 mg/240 mL) temocillin concentrations were tested in triplicate devices with duplicate samples taken at 11 time points during fridge storage and subsequent in-use temperature exposure. RESULT: The percentage of temocillin remaining after 14 days of fridge storage was greater than 97% in both devices and at all concentrations tested. During subsequent in-use temperature exposure, a 95% stability limit was achieved for 12 hours except for the high concentration (25 mg/mL) in the Dosi-Fusor device. It met this criterion for only 10 hours - the percent of temocillin remaining at 12 hours was 94.5%. However, for all devices and the doses tested, the degradation of temocillin was <9% at the end of 24 hours in-use temperature exposure. CONCLUSION: Temocillin reconstituted with 0.3% citrate buffer at pH7 in elastomeric infusion devices can be stored in a fridge (2°C-8°C) for 14 days meeting the YCD acceptance criteria. Considering <5% degradation, the current data supports twice daily dosing of temocillin within the OPAT setting. In jurisdictions where a <10% degradation limit is acceptable, once daily dosing with 24-hour continuous infusion may be considered. Temocillin is a useful alternative to other broad-spectrum anti-Gram-negative agents currently utilised in the OPAT setting and supports the wider antimicrobial stewardship agenda.

Predictors and Outcomes of Healthcare-Associated Infections among Patients with COVID-19 Admitted to Intensive Care Units in Punjab, Pakistan; Findings and Implications.

Healthcare-associated infections (HAIs) have a considerable impact on morbidity, mortality and costs. The COVID-19 pandemic resulted in an appreciable number of hospitalized patients being admitted to intensive care units (ICUs) globally with a greater risk of HAIs. Consequently, there is a need to evaluate predictors and outcomes of HAIs among COVID-19 patients admitted to ICUs. A retrospective study of patients with COVID-19 admitted to ICUs of three tertiary care hospitals in the Punjab province over a five-month period in 2021 was undertaken to ascertain predictors and outcomes of HAIs. Of the 4534 hospitalized COVID-19 patients, 678 were admitted to ICUs, of which 636 patients fulfilled the inclusion criteria. Overall, 67 HAIs were identified among the admitted patients. Ventilator-associated lower respiratory tract infections and catheter-related urinary tract infections were the most frequent HAIs. A significantly higher number of patients who developed HAIs were on anticoagulants (p = 0.003), antithrombotic agents (p < 0.001), antivirals (p < 0.001) and IL-6 inhibiting agents (p < 0.001). Secondary infections were significantly higher in patients who were on invasive mechanical ventilation (p < 0.001), had central venous access (p = 0.023), and urinary catheters (p < 0.001). The mortality rate was significantly higher in those with secondary infections (25.8% vs. 1.2%, p < 0.001). Our study concluded that COVID-19 patients admitted to ICUs have a high prevalence of HAIs associated with greater mortality. Key factors need to be addressed to reduce HAIs.

Hospital Specialist Palliative Care Team Influence on End-of-Life Care in Coronavirus Disease 2019? A Retrospective Observational Cohort Study.

Objectives: The coronavirus 19 disease (COVID-19) pandemic has led to a renewed focus on end-of-life care. The majority of COVID-19 deaths occur in hospital, with patients cared for by generalists and hospital specialist palliative care teams (HSPCTs). This project aims at exploring the potential influences of HSPCTs on end-of-life care in COVID-19. Methods: A retrospective observational study was carried out by exploring four end-of-life care themes in a Scottish hospital population who died from COVID-19. Comparison was made between cohorts seen by HSPCTs versus generalist clinicians. Results: Analysis of 119 patients across NHS Greater Glasgow and Clyde (NHSGGC) health board demonstrated that COVID-19 patients seen by HSPCTs were more likely to be younger (median 77 vs. 81 years; p = 0.02), have a cancer diagnosis (21.7% vs. 5.4%; p = 0.01), die sooner after admission (median four vs. six days; p < 0.01), and be commenced on a syringe driver (89.1% vs. 42.5%; p < 0.01). Differences detected across four end-of-life care themes comparing HSPCTs with generalist teams were minimal with documentation and prescribing in keeping with available guidance. Conclusion: Consistencies in end-of-life care observed across NHSGGC cohorts draw attention to the potential wider impact of HSPCT roles, including education, guideline development, and mentoring. Understanding such diverse effects is important to support funding and development of HSPCTs. Further research is required to better quantify the impact and heterogenous influences of HSPCTs in general.

Optimum length of treatment with systemic antibiotics in adults with dental infections: a systematic review.

Introduction Guidelines on the length of treatment of dental infections with systemic antibiotics vary across different countries. We aimed to determine if short-duration (3-5 days) courses of systemic antibiotics were as effective as longer-duration courses (≥7 days) for the treatment of dental infections in adults in outpatient settings.Methods We searched Ovid Medline, Ovid Embase, Cochrane, trials registries, Google Scholar and forward and backward citations for studies published between database inception and 30 March 2021. All randomised clinical trials (RCT) and non-randomised trials which compared length of treatment with systemic antibiotics for dental infections in adults in outpatient settings published in English were included.Results One small RCT met our defined inclusion criteria. The trial compared three-day versus seven-day courses of amoxicillin in adults with odontogenic infection requiring tooth extraction. There was no significant difference between groups in terms of participant-reported pain or clinical assessment of wound healing.Discussion While a number of observational studies were supportive of shorter-course therapy, only one small RCT concluded that a three-day course of amoxicillin was clinically non-inferior versus seven days for the treatment of odontogenic infection requiring tooth extraction. Limited conclusions on shorter-course therapy can be drawn from this study as all participants commenced amoxicillin two days before tooth extraction which is not common clinical practice. The variability in guidelines for use of antimicrobials in dental infections suggests that guidelines are based on local or national historical practice and indicates the need for further research to determine the optimum length of treatment. RCTs are required to investigate if short-duration courses of antibiotics are effective and to provide evidence to support consistent guidance for dental professionals.

Feedback of Antibiotic Prescribing in Primary Care (FAPPC) trial: results of a real-world cluster randomized controlled trial in Scotland, UK.

OBJECTIVES: To evaluate the effect of general practice-level prescribing feedback on antibiotic prescribing in a real-world pragmatic cluster randomized controlled trial. METHODS: Three hundred and forty general practices in four territorial Health Boards in NHS Scotland were randomized in Quarter 1, 2016 to receive four quarterly antibiotic-prescribing feedback reports or not, from Quarter 2, 2016 to Quarter 1, 2017. Reports included different clinical topics, benchmarking against national and health board rates, and behavioural messaging with improvement actions. The primary outcome was total antibiotic prescribing rate. There were 16 secondary prescribing outcomes and 5 hospital admission outcomes (potential adverse effects of reduced prescribing). The main evaluation timepoint was 1 year after the final report (Quarter 1, 2018), with an additional evaluation in the quarter after the final report (Quarter 2, 2017). Routine administrative NHS data were used to generate the feedback reports and analyse the effects. RESULTS: Total antibiotic prescribing rates were lower at the main evaluation timepoint in both intervention (1.83 versus baseline 1.93 prescriptions/1000 patients/day) and control (1.90 versus baseline 1.98) practices, with no evidence of intervention effect [adjusted rate ratio (ARR) 0.98 (95% CI 0.94-1.02; P = 0.35)]. At the additional timepoint, adjusted total antibiotic prescribing rates were 1.67 and 1.73 prescriptions/1000 patients/day, with evidence of a small intervention effect, ARR 0.99 (0.98-1.00; P = 0.03). CONCLUSIONS: This well-designed, practice-level antibiotic-prescribing feedback had limited evidence of additional effects in the context of decreasing antibiotic prescribing and an established national stewardship programme.

Indications for the use of metronidazole in the treatment of non-periodontal dental infections: a systematic review.

Background: Dental practitioners are the largest prescribers of metronidazole. Antibiotics should only be prescribed when systemic involvement is clear and should be limited to monotherapy with ß-lactams in the first instance. Objectives: To determine whether metronidazole used as monotherapy or in addition to a ß-lactam antibiotic offers any additional benefit over ß-lactam monotherapy in non-periodontal dental infections. Methods: Searches of Ovid Medline, Ovid Embase, Cochrane library and trials registries, forward and backward citations, for studies published between database inception and 2 August 2021. All randomized clinical trials (RCTs) and non-randomized trials comparing either systemic metronidazole monotherapy or metronidazole combined with a ß-lactam with ß-lactam monotherapy for the treatment of non-periodontal dental infections in adults or children in outpatient settings were included. Results: Four publications reporting three RCTs comparing metronidazole with a ß-lactam antibiotic were recovered. Studies were conducted in the 1970s-80s and aimed to demonstrate metronidazole was as effective as penicillin for the treatment of acute pericoronitis or acute apical infections with systemic involvement. Meta-analysis of results was not possible due to differences in measurement of infection signs. All studies concluded that metronidazole and penicillin are equally effective for the treatment of non-periodontal dental infections with systemic involvement. Conclusions: Metronidazole does not provide superior clinical outcomes (alone or in combination with a ß-lactam) when compared with a ß-lactam antibiotic alone for the treatment of non-periodontal dental infections in general dental practice. Guidelines should reinforce the importance of surgical interventions and if appropriate the use of a single agent narrow-spectrum ß-lactam.

Prevalence of bacterial coinfection and patterns of antibiotics prescribing in patients with COVID-19: A systematic review and meta-analysis.

BACKGROUND: Evidence around prevalence of bacterial coinfection and pattern of antibiotic use in COVID-19 is controversial although high prevalence rates of bacterial coinfection have been reported in previous similar global viral respiratory pandemics. Early data on the prevalence of antibiotic prescribing in COVID-19 indicates conflicting low and high prevalence of antibiotic prescribing which challenges antimicrobial stewardship programmes and increases risk of antimicrobial resistance (AMR). AIM: To determine current prevalence of bacterial coinfection and antibiotic prescribing in COVID-19 patients. DATA SOURCE: OVID MEDLINE, OVID EMBASE, Cochrane and MedRxiv between January 2020 and June 2021. STUDY ELIGIBILITY: English language studies of laboratory-confirmed COVID-19 patients which reported (a) prevalence of bacterial coinfection and/or (b) prevalence of antibiotic prescribing with no restrictions to study designs or healthcare setting. PARTICIPANTS: Adults (aged ≥ 18 years) with RT-PCR confirmed diagnosis of COVID-19, regardless of study setting. METHODS: Systematic review and meta-analysis. Proportion (prevalence) data was pooled using random effects meta-analysis approach; and stratified based on region and study design. RESULTS: A total of 1058 studies were screened, of which 22, hospital-based studies were eligible, compromising 76,176 of COVID-19 patients. Pooled estimates for the prevalence of bacterial co-infection and antibiotic use were 5.62% (95% CI 2.26-10.31) and 61.77% (CI 50.95-70.90), respectively. Sub-group analysis by region demonstrated that bacterial co-infection was more prevalent in North American studies (7.89%, 95% CI 3.30-14.18). CONCLUSION: Prevalence of bacterial coinfection in COVID-19 is low, yet prevalence of antibiotic prescribing is high, indicating the need for targeted COVID-19 antimicrobial stewardship initiatives to reduce the global threat of AMR.

Associations between declining antibiotic use in primary care in Scotland and hospitalization with infection and patient satisfaction: longitudinal population study.

BACKGROUND: Reducing antibiotic use is central to antimicrobial stewardship, but may have unintended consequences. OBJECTIVES: To examine associations between size of decline in antibiotic prescriptions in general practices and (i) rate of hospitalization for infection and (ii) patient satisfaction. METHODS: Routine data analysis for all general practices in Scotland, quarter one 2012 (Q1 2012) to quarter one 2018 (Q1 2018). Practices were grouped into quartiles of rate of change in prescribing and changes in rates of hospitalization were compared across groups. For satisfaction analysis, associations between practice-level patient satisfaction in 2017-18 (Scottish Health and Care Experience Survey) and prior change in antibiotic prescription were examined. RESULTS: Antibiotic prescriptions overall fell from 194.1 prescriptions/1000 patients in Q1 2012 to 165.3 in Q1 2018 (14.9% reduction). The first quartile of practices had a non-significant increase in prescriptions [change per quarter = 0.22 (95% CI -0.42 to 0.86) prescriptions/1000 patients], compared with large reductions in the other three groups, largest in quartile four: -2.95 (95% CI -3.66 to -2.24) prescriptions/1000 patients/quarter (29.7% reduction overall). In all quartiles, hospitalizations with infection increased. The increase was smallest in quartile four (the biggest reduction in prescriptions) and highest in quartile one (no significant change in prescriptions): 2.18 (95% CI 1.18 to 3.19) versus 3.68 (95% CI 2.64 to 4.73) admissions/100 000 patients/quarter, respectively [difference = - 1.50 (95% CI -2.91 to -0.10)]. There was no statistically significant association between change in antibiotic prescriptions and patient satisfaction. CONCLUSIONS: Very large reductions in antibiotic prescriptions in Scottish general practices have not been associated with increases in hospitalization with infection or changes in patient satisfaction.

Survey of delivery of parenteral antimicrobials in non-inpatient settings across Europe.

Delivery of parenteral antimicrobials in non-inpatient settings (DPANS) may be through a dedicated outpatient parenteral antimicrobial therapy (OPAT) service, co-ordinated by hospital- or community-based specialised teams, or via an infusion service involving community-based health professionals (nurses, general practitioners) without centralised hospital oversight, or through ad hoc arrangements. DPANS varies among countries. Our objective was to describe how DPANS is organised at a national level in European countries. A survey (65-item self-administered questionnaire) was conducted from February-June 2019 among infection specialists in 34 European countries on behalf of the ESCMID Study Group for Antimicrobial Stewardship (ESGAP) and the British Society for Antimicrobial Chemotherapy (BSAC) OPAT initiative. Most countries (28/34; 82.4%) participated in the survey. DPANS was available in almost all (27/28; 96.4%) responding countries. DPANS was predominantly provided either via specialised OPAT services (17/28; 60.7%) or via infusion services (16/28; 57.1%), with 11 countries (39.3%) providing both services. A formal OPAT team structure with specifically trained staff was reported in only six countries (6/17; 35.3%). Some countries (4/28; 14.3%) had no structured services but practiced DPANS via ad hoc arrangements. The costs of all stages of the process were covered for patients managed by specialised OPAT/infusion services, either completely, partially or for specific patient groups in the majority (20/28; 71.4%) of countries. The main barriers to implement OPAT/infusion services were lack of organisational structure or guidelines. In conclusion, DPANS with respect to availability and organisation is highly heterogeneous in Europe. National/European guidelines may help improve and standardise DPANS.

Assessment of the stability of citrate-buffered piperacillin/tazobactam for continuous infusion when stored in two commercially available elastomeric devices for outpatient parenteral antimicrobial chemotherapy: a study compliant with the NHS Yellow Cover Document requirements.

OBJECTIVES: To investigate the effect of pH control through the use of a citrate-buffered saline diluent pH 7 on the degradation rate of piperacillin/tazobactam solutions for infusion and to determine if an extended shelf-life of up to 13 days fridge 2°C-8°C plus 24 hours 'in-use' at 32°C in two elastomeric devices: FOLFusor LV10 (Baxter Healthcare, Thetford, UK) and Easypump II (B. Braun Medical Ltd, Sheffield, UK) can be achieved. METHODS: Testing was as per the latest National Health Service (NHS) Pharmaceutical Quality Assurance Committee Yellow Cover Document (YCD) requirements.A validated stability indicating high-performance liquid chromatography method was used for assessing the stability of the solutions of piperacillin/tazobactam at a combined concentration of 25 mg/mL and 90 mg/mL respectively. Solutions were tested in two batches in replicate (n=3) at five time points according to the requirements of the YCD. RESULTS: Piperacillin/tazobactam stability was significantly improved when 0.3% w/v citrate-buffered saline pH 7 was used as the diluent, compared with using 0.9% w/v saline as diluent. Greater than 95% of the zero-time concentration of both actives remained following storage at 2°C-8°C for up to 13 days plus 24 hours at 32°C in both devices. The data support extended storage of up to 13 days 2°C-8°C plus 24 hours at 32°C 'in-use' when using FOLFusor LV10 (Baxter) or Easypump II (B. Braun) pump devices. CONCLUSIONS: The enhanced stability complies with UK national standards as stated in the YCD for stability testing of aseptically produced small molecules and supports the storage of piperacillin/tazobactam for up to 13 days 2°C-8°C plus 24 hours at 32°C 'in-use' within two elastomeric pump devices. The extended shelf-life provides a significant advantage over the stability of piperacillin/tazobactam solutions for infusion when reconstituted and diluted in 0.9% w/v saline as diluent. The data open up the possibility of a continuous infusion of piperacillin/tazobactam delivered by elastomeric pump devices over 24 hours in an outpatient parenteral antimicrobial therapy setting.

Co-infections and antimicrobial use among hospitalized COVID-19 patients in Punjab, Pakistan: findings from a multicenter, point prevalence survey.

There are reports of high rates of antibiotic prescribing among hospitalized patients with COVID-19 around the world. To date, however, there are few reports of prescribing in relation to COVID-19 in Pakistan. Herein, we describe a point prevalence survey of antibiotic prescribing amongst patients hospitalized with suspected or proven COVID-19 in Pakistan. A Point Prevalence Survey (PPS) was undertaken in seven tertiary care health facilities in Punjab Provence, Pakistan. Baseline information about antimicrobial use according to the World Health Organization (WHO) standardized methodology was collected on a single day between 5th and 30 April 2021. A total of 617 patients' records were reviewed and 578 (97.3%) were documented to be receiving an antibiotic on the day of the survey. The majority (84.9%) were COVID-19 PCR positive, 61.1% were male and 34.9% were age 36 to 44 years. One quarter presented with severe disease, and cardiovascular disease was the major comorbidity in 13%. Secondary bacterial infection or co-infection (bacterial infection concurrent with COVID-19) was identified in only 1.4%. On the day of the survey, a mean of 1.7 antibiotics was prescribed per patient and 85.4% antibiotics were recorded as being prescribed for 'prophylaxis'. The most frequently prescribed antibiotics were azithromycin (35.6%), ceftriaxone (32.9%) and meropenem (7.6%). The majority (96.3%) of the antibiotics were empirical and all were from WHO Watch or Reserve categories. Overall, a very high consumption of antibiotics in patients hospitalized with suspected or proven COVID-19 was observed in Pakistan and this is concerning in view of already high rates of antimicrobial resistance in the region. Antimicrobial stewardship programs need to urgently address unnecessary prescribing in the context of COVID-19 infection.

Assessment of ceftolozane/tazobactam stability in elastomeric devices and suitability for continuous infusion via outpatient parenteral antimicrobial therapy.

OBJECTIVES: To investigate the stability of ceftolozane/tazobactam 5 mg/mL and 20 mg/mL solutions for infusion in two elastomeric devices: FOLFusor LV10 (Baxter Healthcare) and Easypump® II (B. Braun Medical Ltd) and determine if an extended shelf life of up to 8 days storage at 2-8°C plus 24 h 'in use' at 32°C was achievable. METHODS: Testing was as per the latest NHS Pharmaceutical Quality Assurance Committee Yellow Cover Document (YCD) requirements. A stability-indicating LC method was used for assessing the stability of solutions of ceftolozane/tazobactam at 5 mg/mL and 20 mg/mL (combined concentration of both actives) respectively, tested in two batches in triplicate (n = 3) at five timepoints according to the requirements of the YCD. RESULTS: Ceftolozane/tazobactam, diluted in 0.9% w/v sodium chloride at 5 mg/mL and 20 mg/mL, degraded during in-use storage at 32°C with <95% remaining after 18 h for some device/concentration combinations and all device/concentration combinations at 24 h, respectively. The data does support extended storage of up to 8 days at 2-8°C plus 12 h at 32°C 'in-use' when using either FOLFusor LV10 or Easypump® II devices and is compliant with YCD. CONCLUSIONS: Solutions of ceftolozane/tazobactam can be administered in outpatient parenteral antimicrobial therapy (OPAT) services following refrigerated storage for up to 8 days, when limited to a 12 h infusion at in-use temperature of 32°C. For UK OPAT services where twice daily dosing is feasible, our data provides another treatment option for challenging infections. In countries where a 10% loss of ceftolozane/tazobactam is acceptable, a 24 h infusion is supported by the data.

Strategies to Improve Antimicrobial Utilization with a Special Focus on Developing Countries.

Antimicrobial resistance (AMR) is a high priority across countries as it increases morbidity, mortality and costs. Concerns with AMR have resulted in multiple initiatives internationally, nationally and regionally to enhance appropriate antibiotic utilization across sectors to reduce AMR, with the overuse of antibiotics exacerbated by the COVID-19 pandemic. Effectively tackling AMR is crucial for all countries. Principally a narrative review of ongoing activities across sectors was undertaken to improve antimicrobial use and address issues with vaccines including COVID-19. Point prevalence surveys have been successful in hospitals to identify areas for quality improvement programs, principally centering on antimicrobial stewardship programs. These include reducing prolonged antibiotic use to prevent surgical site infections. Multiple activities centering on education have been successful in reducing inappropriate prescribing and dispensing of antimicrobials in ambulatory care for essentially viral infections such as acute respiratory infections. It is imperative to develop new quality indicators for ambulatory care given current concerns, and instigate programs with clear public health messaging to reduce misinformation, essential for pandemics. Regular access to effective treatments is needed to reduce resistance to treatments for HIV, malaria and tuberculosis. Key stakeholder groups can instigate multiple initiatives to reduce AMR. These need to be followed up.

Safety and efficacy of de-labelling penicillin allergy in adults using direct oral challenge: a systematic review.

BACKGROUND: Approximately 10% of people have an unverified penicillin allergy, with multiple personal and public health consequences. OBJECTIVES: To assess the efficacy and safety of direct oral challenge, without prior skin testing, in this population. METHODS: MEDLINE, EMBASE, CINAHL, the Cochrane Library and Google Scholar were searched from inception to 28 June 2020 (updated November 2020) to find published and unpublished studies that reported direct oral challenge for the purpose of removal of penicillin allergy labels. Population weighted mean was used to calculate the proportion of patients who developed an immediate or delayed reaction to direct oral challenge across the studies. RESULTS: Thirteen studies were included in the review, with a sample size of 1202 (range 7-328). Studies included inpatient and outpatient cohorts assessed as low risk for true allergy. In pooled analysis of all 13 studies there were 41/1202 (3.41%) mild immediate or delayed reactions to direct oral challenge. The population-weighted mean incidence of immediate or delayed reaction to an oral challenge across studies was also 3.41% (95% CI: 2.38%-4.43%). There were no reports of serious adverse reactions, 96.5% of patients could be de-labelled and many were subsequently successfully treated with penicillin. CONCLUSIONS: Direct oral challenge is safe and effective for de-labelling patients assessed as low risk for true allergy. Non-specialist clinicians competent in using an assessment algorithm can offer evaluation of penicillin allergy labels using direct oral challenge in appropriate patients. These measures will facilitate optimal infection treatment for patients, support antimicrobial stewardship, and minimize antimicrobial resistance.