Work

Antibiotic allergy testing improves antibiotic appropriateness in patients with cancer

Year: 2018

Type: article

Abstract: Sir, There is increasing interest in antibiotic allergy testing (AAT) to reduce the burden of patient-reported antibiotic allergies [so-called antibiotic allergy labels (AALs)] with regard to inappropriate prescribing, inferior patient outcomes and antimicrobial resistance.1–3 Recently, AAT programmes have proven successful at ‘de-labelling’ hospitalized patients harbouring penicillin allergies.4–6 However, the greatest prevalence and reported impact of penicillin and other antimicrobial allergies appears to be in cancer patients,7,8 who frequently required antibiotic treatment yet have not been the primary targets of such programmes. We previously published the impact of a multidisciplinary AAT in an antimicrobial stewardship (AMS) programme (AAT-AMS) on prescribing, including a large cohort of actively immunocompromised hosts.6 Whilst this work strengthens the call for AAT-AMS overall, there remains an absence of literature to support AAT in patients with cancer. To further investigate the impact of AAT specifically on cancer patients we utilized the prospective interventional study of AAT-AMS (Austin Health Human Research Ethics Committee number 15/AUSTIN/75),6 examining only patients with a solid organ or haematological malignancy reviewed and tested between the period May 2015 and December 2016 at Austin Health and Peter MacCallum Cancer Centre (Victoria, Australia). Austin Health and the Peter MacCallum Cancer Centre are tertiary referral cancer centres providing care for all cancer and haematological malignancies, including HSCT. Routine antibacterial prophylaxis is not employed and the guideline-preferred agent in febrile neutropenia is piperacillin/tazobactam. Patients underwent antibiotic allergy skin prick, intradermal and/or oral provocation based upon their allergy phenotype [immediate hypersensitivity (IgE) or delayed hypersensitivity (T cell)] as per previously published protocols,6 testing concentrations,9 and for both β-lactam and non-β-lactam hypersensitivities. Testing was carried out preferentially in patients whose neutrophil count had recovered (>0.5 × 109/L) and in whom steroid use was at its lowest possible therapeutic dose (withheld on day of testing). Patients were deemed to have been ‘de-labelled’ if at least one AAL was removed. Post-AAT the electronic medical records were amended, and patients and healthcare providers were provided with written recommendations based on the test results and recommendations for antibiotic usage. Antibiotic appropriateness was defined according to previously published national guidelines utilizing a structured algorithm, a score of 1 or 2 considered ‘appropriate’ and 3 or 4 ‘inappropriate’.10,11 The appropriateness algorithm was developed using an expert consensus approach and is based on a composite assessment of: (i) compliance with national or locally endorsed guidelines; (ii) antimicrobial coverage of causative pathogens; (iii) use of narrow-spectrum antimicrobials when possible; (iv) dosage and/or route; (v) duration if the end date is documented; (vi) allergy mismatch; and (vii) surgical prophylaxis duration <24 h.11 Data collected included baseline demographics, allergy history, infection history, treatment setting (inpatient/outpatient), antibiotic courses (inpatient or outpatient, more than one of dose antibiotic) and antibiotic appropriateness scores for the periods 12 months pre- and 90 days post-AAT-AMS. There were 59 patients with cancer and a history of immune-mediated AAL identified (median age 63 years; IQR 34–79), with the following features: 56% (33/59) were male, median age-adjusted Charlson comorbidity index was 5 (IQR 4–6), 51% (30/59) had a history of haematological malignancy and 14% (8/59) were HSCT recipients. Four patients (7%) died after 90 days of follow-up. For the 59 patients there were 88 individual AALs: 84% (74/88) for β-lactams, 52% (46/88) for penicillin/aminopenicillin, 14% (12/84) for β-lactam/β-lactamase inhibitors, 11% (10/88) for cephalosporins, 8% (7/88) for co-trimoxazole, 5% (4/88) for carbapenems, 3% (3/88) for glycopeptides and 6% (5/88) for others. Skin prick and intradermal testing was undertaken in 55/59 patients, 3 patients had direct oral provocation (with co-trimoxazole) and 6 patients were positive on testing (skin or oral provocation). Comparing antibiotic usage (antibiotic courses) from 12 months pre- to 3 months post-AAT there was a significant increase post-AAT in the proportion of antibiotic courses that were narrow-spectrum penicillins (2% versus 18.2%, P ≤ 0.01), a significant increase post-AAT in the proportion of antibiotic courses that were β-lactam/β-lactamase inhibitor combinations (7.4% versus 22.7%, P ≤ 0.01) and a significant reduction post-AAT in glycopeptide usage (13.5% versus 0%, P ≤ 0.01) (Figure S1, available as Supplementary data at JAC Online), without adverse events or accumulation of new AALs. Utilizing a mixed-effects linear regression model to quantify the association between AAT and antimicrobial courses, adjusting for age-adjusted Charlson comorbidity index, setting (hospital/community) and antibiotic indication, we found that AAT-AMS increased the odds of receiving an appropriate and narrow-spectrum antibiotic therapy, and preferred β-lactam/β-lactamase inhibitors (e.g. piperacillin/tazobactam) utilized in febrile neutropenia (Table 1). Effect of AAT on antibiotic usage If the AAL history was <12 months prior to AAT-AMS, then antibiotic usage data were only collected from a timepoint after the latest ADR. From univariate mixed-effects logistic regression models. From multivariate mixed-effects logistic regression models, controlled for age-adjusted Charlson comorbidity index, infective episode setting (inpatient versus outpatient) and indication category. Such as penicillin VK, penicillin G, amoxicillin, ampicillin or flucloxacillin/dicloxacillin. Narrow-spectrum penicillin or cefalexin or cefazolin. Considered a carbapenem, fluoroquinolone, glycopeptide, lincosamide, lipopeptide, oxazolidinone or third/fourth-generation cephalosporin. Effect of AAT on antibiotic usage If the AAL history was <12 months prior to AAT-AMS, then antibiotic usage data were only collected from a timepoint after the latest ADR. From univariate mixed-effects logistic regression models. From multivariate mixed-effects logistic regression models, controlled for age-adjusted Charlson comorbidity index, infective episode setting (inpatient versus outpatient) and indication category. Such as penicillin VK, penicillin G, amoxicillin, ampicillin or flucloxacillin/dicloxacillin. Narrow-spectrum penicillin or cefalexin or cefazolin. Considered a carbapenem, fluoroquinolone, glycopeptide, lincosamide, lipopeptide, oxazolidinone or third/fourth-generation cephalosporin. Although our study was a non-randomized small study with a selection bias towards those patients requiring antibiotic therapy and only includes those that were reviewed and tested, it strengthens the call for AMS programmes to employ AAT, especially in vulnerable patients, such as those with haematological malignancies. Huang et al.8 previously demonstrated a significant unmet need for AAT services in cancer medicine, identifying 1635 haematology patients over a 5 year period at two centres with an AAL. The increasing life expectancy of cancer sufferers, combined with the cumulative infection risk of cancer therapies and the rise of MDR infections,12 provides a stimulus to ensure AALs do not prevent the delivery of targeted β-lactam antibiotic therapies, instead of frequently employed non-preferred therapies such as carbapenems, fluoroquinolones and lincosamides. Given that many patients may be labelled as β-lactam allergic preceding cancer diagnosis, there remains the broader question of how to develop widely implementable health service programmes that incorporate AAT-AMS into cancer care to reduce AAL impact, and ensure that an AAL is not a barrier to the deployment of appropriate and preferred antibiotics in supportive cancer therapy. This work was supported by the Austin Medical Research Foundation. J. A. T. is supported by a National Health and Medical Research Council (NHMRC) Early Career Fellowship. E. J. P. is supported in part by the National Institutes of Health (NIH) (award numbers 1P50GM115305–01 and 1R01AI103348–01), the NIH-funded Tennessee Center for AIDS Research (P30 AI110527), 1R13 AR071267–01, NHMRC, ACH2 and the Angela Anderson Foundation. A. J. S. is supported by a National Health and Medical Research Council (NHMRC) Early Career Fellowship. None to declare. Figure S1 is available as Supplementary data at JAC Online.

Source: Journal of Antimicrobial Chemotherapy

DOI: 10.1093/jac/dky307

Authors: Jason A Trubiano, M Lindsay Grayson, Elizabeth J Phillips, Andrew J Stewardson, Karin A Thursky, Monica A Slavin