Health outcomes of penicillin allergy testing in children: a systematic review.

BACKGROUND: Penicillin allergy labels are commonly acquired in childhood and lead to avoidance of first-line penicillin antibiotics. Understanding the health outcomes of penicillin allergy testing (PAT) can strengthen its place in antimicrobial stewardship efforts. OBJECTIVES: To identify and summarize the health outcomes of PAT in children. METHODS: Embase, MEDLINE, Web of Science, Cochrane Library, SCOPUS and CINAHL were searched from inception to 11 Oct 2021 (Embase and MEDLINE updated April 2022). Studies that utilized in vivo PAT in children (≤18 years old) and reported outcomes relevant to the study objectives were included. RESULTS: Thirty-seven studies were included in the review, with a total of 8411 participants. The most commonly reported outcomes were delabelling, subsequent penicillin courses, and tolerability to penicillin courses. Ten studies had patient-reported tolerability to subsequent penicillin use, with a median 93.6% (IQR 90.3%-97.8%) of children tolerating a subsequent course of penicillins. In eight studies, a median 97.3% (IQR 96.4%-99.0%) of children were reported as 'delabelled' after a negative PAT without further definition. Three separate studies verified delabelling by checking electronic or primary care medical records, where 48.0%-68.3% children were delabelled. No studies reported on outcomes relating to disease burden such as antibiotic resistance, mortality, infection rates or cure rates. CONCLUSIONS: Safety and efficacy of PAT and subsequent penicillin use was the focus of existing literature. Further research is required to determine the long-term impact of delabelling penicillin allergies on disease burden.

Optimization of antimicrobial dosing in patients with acute kidney injury: a single-centre observational study.

Background: Acute kidney injury (AKI) is a potential complication of systemic infection. Optimizing antimicrobial dosing in this dynamic state can be challenging with sub- or supra-therapeutic dosing risking treatment failure or toxicity, respectively. Locally, unadjusted renal dosing for the first 48 h of infection is recommended. Objectives: To determine the outcomes associated with this dosing strategy. Methods: A retrospective cohort analysis was undertaken in patients treated for Gram-negative bacteraemia with concurrent non-filtration dependent AKI from a single-centre NHS acute hospital (April 2016-March 2020). Patient demographics, microbiology data, antimicrobial treatment and patient outcome (in-hospital mortality and kidney function) were analysed. Results: In total, 647 episodes of Gram-negative bacteraemia (608 patients) were included; 305/608 (50.2%) were male with median age 71 years (range 18-100). AKI was present in 235/647 (36.3%); 78/647 (12.1%) and 45/647 (7.0%) having Kidney Disease Improving Global Outcomes-defined injury (stage 2) or failure (stage 3), respectively. In-hospital 30 day mortality was 25/352 (7.1%), 14/112 (12.5%), 26/123 (21.1%) and 11/60(18.3%) in patients with normal renal function, AKI stage 1, AKI stage ≥2 and established chronic kidney disease, respectively. Recovery of renal function at Day 21 or discharge was present in 105/106 surviving patients presenting with AKI stage ≥2. Time to recovery of AKI was similar in patients receiving full, low or no aminoglycoside (3 versus 4 versus 3 days, P = 0.612) and those receiving full- and low-dose ß-lactam (3 versus 5 days, P = 0.077). Conclusions: There is a high burden of AKI in patients with Gram-negative bacteraemia. Dose adjustments of ß-lactams may not be necessary in the first 48 h of infection-induced AKI and single-dose aminoglycosides may be considered for early empirical coverage.

Burden of enteral supplement interactions with common antimicrobial agents: a single-centre observational analysis.

INTRODUCTION: Oral antimicrobials, including ciprofloxacin, levofloxacin and doxycycline, are susceptible to binding with enteral therapies such as calcium and iron therapies. Administered together, the bioavailability of these antimicrobials is expected to be reduced. METHODS: A retrospective case series of patients receiving oral antimicrobials (ciprofloxacin, levofloxacin and doxycycline) was analysed at a single-centre NHS acute hospital (April 2016-September 2019). Patient demographics, including concurrent enteral therapies, were recorded using medical records. Clinically important interactions were defined as doses administered within 2 hours of antimicrobial therapy. RESULTS: A total of 4067 prescriptions for the study antimicrobials (ciprofloxacin, n=1905; levofloxacin, n=538; and doxycycline, n=1624) were prescribed for 3584 patients. 1918/3583 (53.5%) of the patients were female, and the median age was 67 years (range 0.5-105.0 years). 810/4067 (19.3%) prescriptions reviewed had an interacting enteral therapy (calcium or iron salt) administered within 2 hours of the study medication. CONCLUSION: The concomitant administration of enteral calcium and iron with oral antimicrobials is common within the acute care hospital setting. Approximately one in five patients has a clinically important interaction which may impair oral bioavailability and limit treatment efficacy. As antimicrobial stewardship teams strive for increased intravenous-to-oral de-escalation, it is important that optimum dosing administration is followed to optimise patient outcomes.

Clinical outcomes of temocillin use for invasive Enterobacterales infections: a single-centre retrospective analysis.

BACKGROUND: With increasing frequency of resistant Gram-negative bacteria, temocillin has potential utility in reducing carbapenem use. The 2020 EUCAST guideline changes temocillin breakpoints and reclassifies isolates with an MIC of 0.001-16 mg/L as 'susceptible, increased exposure' necessitating 6 g/day rather than the previous 4 g/day, associated with significant cost implications. OBJECTIVES: We explore the clinical utility and treatment failure rate of temocillin at 4 g/day dosing. METHODS: All adult inpatient electronic prescriptions of temocillin (3 days or greater) from March 2016 to October 2019 were retrieved using a clinical decision support system (ICNET®). Treatment success was defined as survival, no switch to broad-spectrum agent for the same indication and no subsequent recrudescence of infection, occurring within 30 days. RESULTS: Temocillin was used in 205 eligible patient-episodes, median age 79 years (IQR : 71-87 years), 42.4% female. Median temocillin course length was 5.9 days (IQR : 4.6-7.8 days). Indications for use: urinary tract infection (UTI) (n = 141), pneumonia (n = 53), other (n = 11). In total, 144 (70.2%) patients had targeted treatment; 74 (36.1%) against Escherichia coli, 70 (34.4%) other Enterobacterales. A total of 130 (63%) patients received 4 g/day; the remaining patients had reduced renal function with dosing in accordance with guidance. Overall temocillin treatment success was 79.5%; highest when used to treat UTI 85.8% (versus 67.9% in respiratory infections, P = 0.008). Empirical treatment demonstrated 82.0% (50/61) success [versus 78.5% (113/144) among targeted treatment, P = 0. 71]. CONCLUSIONS: Temocillin at 4 g/day is an effective and safe alternative in treating patients with Gram-negative infections, but should be considered in the context of patient age and comorbidities. Increased dosing or alternate strategies may be indicated when the infection is not of a urinary source.

Evaluation of a thrice weekly administration of teicoplanin in the outpatient setting: a retrospective observational multicentre study.

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.

Treating infections caused by carbapenemase-producing Enterobacterales (CPE): a pragmatic approach to antimicrobial stewardship on behalf of the UKCPA Pharmacy Infection Network (PIN).

The emergence of carbapenemase-producing Enterobacterales (CPE) as a major cause of invasive infection both within the UK and internationally poses a very real concern for all providers of healthcare. The burden of morbidity and mortality associated with CPE infections is well described. The need for early, targeted, effective and safe antimicrobial therapy remains key for the management of these infected patients yet reliable antimicrobial treatment options remain scarce. In the absence of a universal treatment for these CPE invasive infections, individual treatment options tailored to susceptibilities and severity of infection are required. This working group from within the UK Clinical Pharmacy Association (UKCPA) Pharmacy Infection Network has developed evidence-based treatment recommendations to support infection specialists in managing these complex infections. A systematic review of peer-reviewed research was performed and analysed. We report consensus recommendations for the management of CPE-associated infections. The national expert panel makes therapeutic recommendations regarding the pharmacokinetic and pharmacodynamic properties of the drugs and pharmacokinetic targets, dosing, dosage adjustment and monitoring of parameters for novel and established antimicrobial therapies with CPE activity. This manuscript provides the infection specialist with pragmatic and evidence-based options for the management of CPE infections.

Evaluating the impact of the ICNET® clinical decision support system for antimicrobial stewardship.

Background: Antimicrobial resistance (AMR) is an ecological and economic crisis and stewardship of available antimicrobials is required. Electronic prescribing, where available, enables auditing of practice, yet in order to be efficient and effective in addressing inappropriate antimicrobial prescribing, better use of current and new technological interventions is needed. This retrospective observational evaluation looked at the impact of a commercial clinical decision support system (CDSS) on the workflow of an established antimicrobial stewardship (AMS) team. Material/methods: Clinical, workflow, and pharmaceutical data from 3 months post implementation of CDSS were collated, and compared to the same 3 month periods in preceding years. The evaluation considered total interventions made, the types of intervention made, impact of said interventions, and time spent executing interventions. All antimicrobial data were adjusted for total daily defined doses (DDD) of intravenous antimicrobials. Results: Productivity: In the 3 month evaluation period (Jun-Aug 2016) a total of 264 case reviews resulting in 298 AMS interventions were made. Compared to preceding years where 138 and 169 interventions were made (2013 and 2014 respectively). In 2013 49% of interventions were stopping medication and 30% change of therapy based on cultures and sensitivities compared to 25 and 17% in 2016. In contrast to previous years', the CDSS instead enabled a greater number of dose/drug optimisation (13%), escalation of antimicrobials (12%) and intravenous (IV) to oral switch (11%) interventions.Patient Identification: Despite increased patient numbers post-CDSS, on average 46 min per day was spent compiling a patient list for review, compared to 59 min in 2014. The use of CDSS facilitated 15 interventions/1000DDD, compared to pre-intervention (9.4/1000DDD in 2013; 11.5/1000DDD in 2014). Conclusions: Initial evaluation of the impact of this CDSS on AMS at the organisation has demonstrated effectiveness in terms of case finding, AMS team productivity, and workflow auditing. More importantly, patient infection management has been optimised with a shift in the emphasis of AMS interventions. It has contributed to the success of the healthcare provider achieving nationally set remunerated AMS targets.

Once-daily tigecycline for outpatient parenteral antibiotic therapy: a single-centre observational study.

BACKGROUND: Tigecycline has potential utility in the treatment of complex polymicrobial infections or those caused by MDR organisms in the ambulatory care setting owing to its breadth of antimicrobial coverage. Whilst licensed for twice-daily IV administration, its long half-life permits once-daily administration, which may facilitate successful outpatient parenteral antibiotic therapy (OPAT). METHODS: A retrospective case series of patients receiving once-daily tigecycline under OPAT was analysed at a single-centre NHS acute hospital (January 2016-June 2018). Patient demographics, including comorbidities, antimicrobial indication, concurrent antimicrobial therapies, treatment duration and adverse events related to treatment were recorded using medical records. Treatment outcomes were defined using the BSAC National Outcomes Registry System (NORS). RESULTS: A total of 25 treatment episodes (24 individual patients) were analysed. The most common indications were bone and joint infections (n = 8) and intra-abdominal infections (n = 7). MDR organisms were common, including ESBL-producing Enterobacterales (n = 13) and glycopeptide-resistant enterococci (n = 4). Median treatment duration was 18 days. Nineteen of 25 (76%) cases had complete cure of treatment, 3 patients experienced treatment-related adverse reactions necessitating cessation of therapy and 3 experienced failure due to disease progression. Eight patients experienced non-limiting adverse effects, such as nausea, vomiting and rash, and one patient had a transient rise in amylase 3 times the upper normal limit (with no evidence of pancreatitis). CONCLUSIONS: Once-daily tigecycline can be successfully used for management of complex infections in the OPAT setting, with predominantly mild adverse effects, which can be managed with antiemetics or slow administration.

Deprescribing medicines in the acute setting to reduce the risk of falls.

BACKGROUND: Falls are a common cause of morbidity and hospitalisation in older people. Inappropriate prescribing and polypharmacy contribute to falls risk in elderly patients. This study's aim was to quantify the problem and find out if medication review in the hospital setting led to deprescribing of medicines associated with falls risk. METHODS: Admissions records for elderly patients were examined to identify those whose presenting complaint included a fall. Inpatient medication charts, pharmaceutical care notes, medical notes and discharge summaries were examined to identify any falls-risk medicines from admission histories and to determine if any medication review took place, and whether or not changes were made as a result. In particular deprescribing and dose reduction details were analysed. RESULTS: 100 patients over 70 years old were admitted following a fall during the 2 months study period. The mean number of medicines on admission was 6.8 per patient with polypharmacy found in 62/100 (62%). One or more falls-risk medicine was found in 65/100 (65%) patients. Medicines review was carried out in 86/100 (86%) of patients, and 59/697 (8.5%) medicines were deprescribed. Pharmacist involvement in medication review led to a significant reduction in the number of falls-risk medicines per patient (p=0.002). CONCLUSIONS: Inappropriate prescribing and polypharmacy are found frequently in elderly patients at admission following a fall. Comprehensive medicines reviews should be carried out in all such patients with the objective of deprescribing or reducing doses to minimise risk of harm. Involvement of a pharmacist improves the rate of reduction of falls-risk medicines.