Table 4.
Characteristics of studies included in the systematic review.
| Author, Year | Country | Period of Observation and Study Design | Participating Centres |
Patients’ Selection | Age and Sex | Total of Patients | ED Visits for Allergy or Anaphylaxis | Drug-Related Allergy or Anaphylaxis | Hospitalization for Drug-Related Allergy or Anaphylaxis | Causative Drug Classes |
|---|---|---|---|---|---|---|---|---|---|---|
| Asai, 2014 [21] | Canada | 2011–2012 Retrospective single centre study |
Adult tertiary care ED | Diagnosis of anaphylaxis or allergic reactions (ICD-10 codes) | Median (IQR): 31.5 (26.4–44.0) years Females 66.3% |
37,730 | 98 | 18 | NR | Amoxicillin 16.7% |
| Banerji, 2014 [22] | USA | 2006–2008 Retrospective database analysis |
Truven Health MarketScan Commercial and Medicare Supplemental Databases (Truven, Ann Arbor, Mich) | Diagnosis of anaphylaxis (ICD9-CM codes) | Mean ± SD 48 ± 19 years Females 71% |
716 | 716 | 716 | 205 | NR |
| Bellou, 2003 [52] | France | 1 year (1998) Retrospective single centre study |
General hospital ED | Cases of suspected allergic reaction | Mean ± SD 55 ± 18.5 years Females 51% |
324 | 324 | 25 | Overall, 90 | Beta-lactams 28% Macrolides 20% NSAIDs 52% |
| Bielen, 2019 [53] | Croatia | 2012–2015 Retrospective single centre study |
Tertiary care university hospital ED | Cases of hypersensitivity (SMQ) | <29 years: 8005 30–39 years: 7875 40–49 years: 8095 50–64 years; 17611 65–74 years: 13414 >75 years: 16982 Females 54.6% |
71,982 | 3039 | 627 | 38 | Antibiotics 44.7% Analgesics and NSAIDs 18.7% |
| Budnitz, 2005 [23] | USA | 3 months Retrospective multicentre study; database analysis |
NEISS-CADES database | Cases of ADE | <2 years: 56; 2–9 years: 62; 10–19 years: 44; 20–29: 66; 30–39 years: 59; 40–49 years: 84; 50–59 years: 65; 60–69 years: 57; 70–79: 58; ≥80 years: 47 Females 63.9% |
598 | 155 | 155 | 4 | Antibiotics 42.9% Non-opioid analgesics 29.3% Cardiovascular agents 24% |
| Budnitz, 2006 [24] | USA | 2004–2005 Retrospective multicentre study; database analysis |
NEISS-CADES database | Cases of ADE | 0–4 years: 104,185; 5–17 years: 225,082; 18–44 years: 362,044; 45–64: 147,178; ≥65 years: 83,549 Females 44.7% |
701,547 estimated annual ED visits | 235,202 estimated annual ED visits | 235,202 estimated annual ED visits | 13,232 estimated annual ED visits | NR |
| Budnitz, 2011 [25] | USA | 2007–2009 Retrospective multicentre study; database analysis |
NEISS-CADES database | Cases of ADE | 65–69 years: 2470; 70–74 years: 1840; 75–79 years: 2629; 80–84 years: 2476; ≥85 years: 2621 Females 59% |
265,802 estimated annual ED visits | 39,455 estimated annual ED visits |
39,455 estimated annual ED visits |
5617 estimated annual hospitalization | Cardiovascular agents Antibiotics |
| Cho, 2019 [42] | Korea | 2012–2016 Cross-sectional multicentre study |
7 community hospitals EDs | Cases of anaphylaxis (ICD-10 codes) | Mean ± SD 51.5 ± 16.0 Females 34.7% |
325,857 | 1021 | 135 | NR | NSAIDs 28.1% Antibiotics 15.6% Antibiotics and NSAIDs 3.7% Radiocontrast media 2.2% |
| Cianferoni, 2001 [54] | Italy | 1985–1996 Retrospective chart review |
University hospital ED | Diagnosis of acute anaphylaxis | Mean ± SD 42 ± 18 Females 45% |
113 | 113 | 52 | NR | Antibiotics 48% NSAIDs 35% |
| Cohen, 2008 [26] | USA | 2004–2005 Retrospective multicentre study; database analysis |
NEISS-CADES database | Cases of ADE | <1 year: 386; 1–4 years: 703; 5–8 years: 302; 9–12 years: 216; 13–18 years: 475 Females NR |
6681 | 2802 | 2802 | Overall, 5.1 | Antibiotics 60.8% Analgesics 9.2% Multiple agents 6.7% Respiratory medications 5.9% Psychotropic medications 2.2% |
| Cohen, 2018 [43] | Israel | 2013–2016 Retrospective single centre study |
Paediatric hospital ED | Cases of allergic reactions or anaphylaxis (Anaphylaxis Criteria, Sampson et al.) | Mean 6.8 years (range 0–16 years) Females 34.7% |
113,067 | 428 | 10 | 8 (1 of which in ICU) | NR |
| Dennehy, 1996 [27] | USA | 30 days (1994) Single centre study |
General hospital ED | Cases of drug-related illness | Mean ± SD 41.7 ± 22.5 years Females 50% |
50 | 7 | 7 | Overall, 8 | NR |
| Gabrielli, 2018 [28] | Canada | 2012–2016 Retrospective/prospective multicentre study |
3 paediatric hospital and 1 general hospital EDs | Cases of anaphylaxis (diagnosis at ED presentation or ICD codes) | Median 49.4 (IQR 40.1–62.9) adults; median 8.00 (IQR 3.79–15.36) children Females: 71.9% adults; 47.1% children |
884,000 | 1913 | 115 (64 adults; 51 children) | Admitted (5/51 = 9.8% children, 3/64 = 4.7% adults) Admitted ICU (1/51 = 2.0% children, 1/64 = 1.6% adults) Admitted hospital ward (4/51 = 7.8% children, 2/64 = 3.1% adults) |
Beta-lactams (28.1% adults, 31.4% children) Quinolones (20.3% adults, 2% children) Other antibiotics (6.3% adults, 0% children) NSAIDs (20.3% adults, 21.6% children) Radiocontrast media (3.1% adults, 3.9% children) |
| Goh, 2018 [44] | Singapore | 2014–2015 Prospective multicentre study |
3 general hospital EDs | Cases of anaphylaxis (ICD-9 codes) | Median 23 years (range 3 months to 88 years and 9 months) Females 49.1% |
7373 | 426 | 85 (66 adults; 19 children) | 3 | NSAIDs (24.2% adults, 52.6% children) Antibiotics (21.2% adults, 5.3% children) Paracetamol (3.0% adults, 10.5% children) |
| Grunau, 2015 [29] | USA and Canada | 2007–2012 Retrospective multicentre cohort study |
2 teaching hospital EDs | Diagnosis of allergic reaction | Median (IQR): 34 (27–47) years patients treated with steroids; 35 (26–49) years patients treated without steroids Females 60.9% |
2701 | 2701 | 702 | 11 | Anti-infective agents 48.9% Nervous system agents 10.3% (analgesics 2%) Radiocontrast media 3.7% NSAIDs 2.4% |
| Hall, 2020 [57] | Australia | 2010–2015 Retrospective multicentre cohort study |
5 university tertiary hospital EDs | Cases of antimicrobial anaphylaxis (ICD-10 codes) | Median 51 years (IQR 36–67) Females 61% |
293 | 185 | 185 | 7 ICU admission | Overall (out of 185) Penicillins 39.9% Cephalosporins 35.1% Amino-penicillins 18.5% Amino-cephalosporins 17.0% |
| Hampton, 2014 [30] | USA | 2009–2011 Retrospective multicentre study; database analysis |
Administrative database 63 centres |
Cases of psychiatric medication-related ADE | 19–44 years: 49.4 (46.5–52.4) 45–64 years: 33.3 (30.7–35.9) ≥65 years: 17.3 (14.7–19.8) Females 61.9% |
89,094 estimated annual ED visits | 11,493 estimated annual ED visits | 11,493 estimated annual ED visits | Overall, 17,188 estimated annual hospitalization | Zolpidem Quetiapine Alprazolam Lorazepam Haloperidol Clonazepam Trazodone Citalopram Lithium Risperidone |
| Han, 2018 [45] | Korea | 2009–2014 Retrospective cohort study; database analysis |
National insurance claim database of the Health Insurance Review and Assessment (HIRA) | Cases of drug hypersensitivity reactions (ICD-10 codes) | 88,003 ≤19 years 169,103 20–44 years 180,535 45–64 years 97,408 ≥65 years Females 57.5% |
535,049 | 3984 (T88.6 code) | 3984 (T88.6 code) | 184 (T88.6 code) | NR |
| Harduar-Morano, 2011 [31] | USA | 2005–2006 Retrospective multicentre study |
General hospital EDs | Diagnosis of anaphylaxis (ICD9-CM codes) | Mean ± SD 38.7 ± 21.46 Females 57% |
2751 | 2751 | 228 | 54 | NR |
| Hitti, 2015 [46] | Lebanon | July–December 2009 Retrospective single centre study |
Tertiary care centre ED | Cases of acute allergic reaction (ICD-9 codes) | Mean ± SD 31.8 ± 19.2 years Females 42% |
293 | 245 | 58 | Overall, 1 patient was hospitalized | Antibiotics 8.2% NSAIDs 4.9% |
| Hsin, 2011 [47] | India | 2000–2010 Retrospective single centre cohort study |
General hospital ED | Diagnosis of anaphylaxis (ICD9 codes) | Mean age overall 43.3 years Female 47% |
201 | 86 | Overall, 161 | NR | NSAIDs Antibiotics Chemotherapy Anti-epileptics Contrast media Immunotherapy Biologics H1N1 Vaccine Anaesthesia |
| Huang, 2012 [32] | USA | 2004–2008 Retrospective single centre study |
Paediatric hospital ED | Cases of anaphylaxis | Median (IQR) 8 (4 months–18 years) years Females 49% |
192 (20 had multiple reactions) | 192 | 19 | Overall, 28 | NR |
| Jones, 2013 [33] | USA | 2004–2013 Retrospective multicentre study; database analysis |
NEISS-CADES database | Cases of fluoroquinolone-associated hypersensitivity ADEs | Mean age overall 48.22 years Females 73.7% |
102,536 | 1659 | 1422 | 96 | Ciprofloxacin Levofloxacin Moxifloxacin Gemifloxacin Ofloxacin |
| Kim MY, 2018 (a) [48] | Korea | 2011–2013 Retrospective multicentre study |
2 tertiary hospitals and 1 secondary hospital EDs | Cases of anaphylaxis (ICD codes) | Mean ± SD 46 ± 17.1 Females 55.2% |
194 | 194 | 151 | NR | Antibiotics Acetylsalicylic acid Radiocontrast media NSAIDs |
| Kim MY, 2018 (b) [49] | South Korea | 2003–2016 Retrospective single centre study |
Tertiary university hospital ED | Cases of anaphylaxis (Korean Standard Classification of Disease) | Mean ± SD 41.1 ± 23.4 Females 48.2% |
199 | 199 | 72 | 13 | Overall (out of 199) Antibiotics 40.2% NSAIDs 33.3% Radiocontrast media 11.1% |
| Ko, 2015 [50] | Korea | 2007–2014 Single centre study |
Tertiary teaching hospital ED | Cases of anaphylaxis (Skin or mucosal tissue involvement; Respiratory compromise; Systolic blood pressure <90 mmHg or syncope; Gastrointestinal symptoms) | Mean ± SD 48.4 ± 15.7 years Females 54.9% |
655 | 415 | 187 | Overall, 3 patients were hospitalized | Radiocontrast media 70 NSAIDs 39 Cephalosporins 34 Anticancer agents 16 |
| Losappio, 2014 [55] | Italy | 2011 Retrospective single centre study |
General hospital ED | Cases of allergic urticaria (ICD-9 codes) | Mean 35.4 years (range 0–90 years) Females 49.2% |
44,112 | 459 | 92 (79 adults; 13 children) | NR | NSAIDs Beta-lactams |
| Lovegrove, 2011 [34] | USA | 2006–2009 Retrospective multicentre study |
Drug Abuse Warning Network (DAWN), 250 non-federal, short-stay general hospitals | Cases of antivirals-related ADE | <6 years: 139; 6–11 years: 103; 12–17 years: 58; 18–44 years: 332; 45–64 years: 161; ≥65 years: 89 Female 59.3% |
879 | 274 | 274 | Overall, 125 | Amantadine Rimantadine Oseltamivir Zanamivir |
| Lovegrove, 2019 [35] | USA | 2011–2015 Retrospective multicentre study; database analysis |
NEISS-CADES database | Cases of antibiotics-related ADE in children (MedDRA) | 2870 < 1–2 years 743 3–4 years 1187 5–9 years 1742 10–19 years Females 52.1% |
6542 | 5763 | 5763 | Overall, 265 | Overall (out of 6542) Penicillins 59.7% Cephalosporins 11.2% Sulfonamides 9.5% |
| Motosue, 2018 (a) [36] | USA | 2005–2014 Prospective observational study; database analysis |
OLDW administrative database | Cases of anaphylaxis (ICD-9 codes) | Median 36 years (interquartile range 17–52) Females 57.5% |
56,212 | 56,212 | 6720 | Inpatient 717 and ICU 409 | NR |
| Motosue, 2018 (b) [37] | USA | 2008–2012 Retrospective study; database analysis |
Administrative claims database (OptumLabs Data Warehouse) |
Cases of anaphylaxis and anaphylactic shock (ICD-9 codes) | Median 42 years (range 1–87 years) Females 58.3% |
7367 | 7367 | 1076 | Overall, 532 ICU admission | NR |
| Quiralte, 1997 [56] | Spain | 1992–1995 Prospective single centre study |
University hospital ED | Cases of NSAIDs-related anaphylaxis | Mean ± SD 35.7 ± 13.9 Females 71% |
21 | 21 | 21 | NR | Dipyrone 57.1% Propyphenazone 14.2% Acetic derivatives (diclofenac and indomethacin) 14.2% |
| Rangkakulnuwat, 2020 [51] | Thailand | 2007–2016 Retrospective single centre study |
University hospital ED | Cases of anaphylaxis (ICD-10 codes) | Median 24.0 years (IQR 19.0–43.0) Females 57.2% |
10,848,695 | 441 | 79 | NR | NSAIDs 7.4% Antimicrobial Agents 4.0% Radiocontrast media 0.9% |
| Russell, 2010 [38] | USA | 2002–2006 Retrospective single centre cross-sectional study |
Tertiary care paediatric hospital ED | Diagnosis of anaphylaxis (ICD-9 codes) | Mean ± SD 9.49 ± 5.56 Females 36% |
103 | 103 | 15 | 4 | Antibiotics Intravenous contrast |
| Schneitman Mcintire, 1996 [39] | USA | 1992–1993 Retrospective single centre study |
General hospital ED | Patients who experienced medication misadventures | 15–44 years 38% 65 years or older 33% Females 62% |
62,216 | 221 | 204 | 7 | Trimetoprim sulfametoxazol 34% Amoxicillin 21% Ibuprofen 5.4% |
| Shehab, 2008 [40] | USA | 2004–2005 Retrospective multicentre study; database analysis |
NEISS-CADES database | Cases of antibiotics-related ADE | <1 years: 545; 1–4 years: 976; 5–14 years: 656; 15–44 years: 2577; 45–64 years: 1143; 65–79 years: 507; ≥80 years: 210 Females 64.4% |
142,505 estimated annual ED visits | 112,116 estimated annual ED visits |
112,116 estimated annual ED visits |
8738 estimated annual hospitalization |
Penicillins 36.9% Cephalosporins 12.2% Fluoroquinolones 13.5% Sulfonamide trimethoprim 11.8% Macrolides and Ketolides 6.9% Tetracyclines 3.1% Vancomycin Linezolid 0.8% |
| Willy, 2009 [41] | USA | 2004–2005 Retrospective multicentre study; database analysis |
NEISS-CADES database | Cases of analgesics-related ADE | 0–9 years: 32,222; 10–19 years: 17,012; 20–29 years: 28,298; 30–39 years: 23,165; 40–49 years: 22,706; 50–59 years: 18,767; 60–69 years: 14,590; 70–79 years: 15,030; 80–89 years: 14,933; ≥90 years: 1998 Females 57% |
188,721 | 58,101 | 58,101 | Overall, 22,646 | Acetaminophen Non-narcotic-acetaminophen combination Narcotic- acetaminophen combination Acetylsalicylic acid Ibuprofen Naproxen |
ADE: adverse drug event; ED: emergency department; ICD-CM: International Classification of Diseases-Clinical Modification; ICU: intensive care unit; IQR: interquartile range; MedDRA: Medical Dictionary for Regulatory Activities Terminology; NR: not reported; NSAIDs: non-anti-inflammatory drugs; SD: standard deviation; SMQ: standardized MedDRA query; T88.6 code: Anaphylactic shock due to adverse effect of correct drug or medication properly administered.