Infection Control & Hospital Epidemiology
(ICD-9-CM) diagnostic codes (Table 1). ADE codes were selected from an extensive list of the National Expert Panel of the ICD-9- CM Adverse Event Classification, Utah/Missouri Patient Safety Consortium and from codes used by our active hospital phar- macovigilance program to identify ADEs.7,8 Those codes con- sidered pertinent to antibiotic-associated ADEs were included. Patients who had an ADE-associated ICD-9 code or E-code at either the point of discharge following the initial surgical proce- dure or during a subsequent hospitalization (if readmission occurred within 48 hours of the initial surgical procedure) were considered to have potentially experienced a perioperative ADE.
Data analysis
The association of penicillin ADR status with intraoperative antibiotic selection and perioperative ADEs was determined using categorical analysis; the Fisher exact test was used to determine statistical significance. A multivariable logit model was developed to determine the odds of receiving a drug other than cefazolin, adjusting for MRSA isolation and surgical wound class. All ana- lyses were completed using Stata version 14 software (StataCorp, College Station, TX).
Results
In total, 17,741 operations with intraoperative AP were identified. We excluded 382 operations (2.2%) due to a documented cephalosporin allergy. These patients were predominately male (56%) and white (69%), with a median age of 7.6 years
Table 1. International Classification of Diseases, Ninth Revision, Clinical Mod- ification (ICD-9-CM) Codes Used to Identify Perioperative Adverse Drug Effects
ICD-9-CM 283.9
288.03 693.0 695.1 708.0 708.9 782.1 995
995.1 995.2
995.27 995.3
e94.60
960–961, E856–857
Description
Acquired hemolytic anemia Drug induced neutropenia Drug dermatitis
Erythema multiforme Allergic urticaria Urticaria nosa
Nonspecific skin eruption Other anaphylactic reaction Angioneurotic edema
Unspecified adverse effect of unspecified drug, medicinal and biological substance
Other drug allergy Allergy, unspecified
Local anti-infectives and anti-inflammatory drugs causing adverse effects in therapeutic use
Poisoning by antibiotics and other anti-infectives
E930–E931 Adverse effects of antibiotics and other anti-infectives aNot otherwise specified.
Discussion
Surgical antibiotic prophylaxis results in significant antibiotic exposure among children.6,9 Despite evidence that cefazolin is safe to use in children with a non–life-threatening penicillin ADR history, many clinicians remain reluctant. Ideally, cefazolin would be selected when indicated because it is narrow-spectrum and well tolerated and has been extensively studied. Our results demonstrate that prescribers avoid cefazolin in children labeled with a penicillin ADR, regardless of the severity of the reaction. Additionally, alternative antibiotics such as vancomycin were associated with higher rates of perioperative ADRs compared to cefazolin. In this study, penicillin ADR(+) patients received an alter-
native agent instead of cefazolin in 72% of cases. This is consistent with Beltran et al9 who reported that ADR(+) children received cefazolin in only 20% of cases. We observed that penicillin ADR classification and severity did not influence antibiotic choice, suggesting that providers are not relying on ADR history to guide antibiotic selection. Clindamycin was the most common cefazolin alternative selected. Unfortunately, clindamycin has limitations due to rising resistance, making it potentially ineffective against methicillin-susceptible S. aureus for which cefazolin would be 100% effective.10 Only 1% of penicillin ADR(+) patients who received cefazolin experienced a perioperative ADE, which is consistent with pre- vious findings.9 Our data reveal that perioperative ADEs occurred
1481
(interquartile range [IQR], 2.3–13.4). Most wounds were classified as clean (66%) or clean-contaminated (28%). The most common procedures were closed reduction of the elbow with percutaneous pinning, removal of hardware, and laparoscopic-assisted gastro- stomy. A penicillin ADR label (allergy or hypersensitivity or side effect) was documented in 1,150 cases (6.6%). The prevalence of cefazolin administration in ADR negative (−) cases was sig- nificantly higher (86%) compared to ADR positive (+) allergy or hypersensitivity cases (28%; P < .001) or ADR(+) side-effect cases (48%; P < .001). After adjusting for MRSA isolation and wound class, the odds of receiving an alternative agent compared to ADR(−) cases, was significantly higher in ADR(+) allergy or hypersensitivity cases (25.4; 95% confidence interval [CI], 21.8– 29.6) and ADR(+) side-effect cases (6.4; 95% CI, 3.8–11.0). Penicillin ADR severity had no effect on the likelihood of receiving an alternative to cefazolin. Clindamycin was the most commonly prescribed alternative
antibiotic prophylaxis among ADR(+) patients at 58.4%. This was significantly higher compared to ADR(−) patients (5.3%; P < .001). Penicillin ADR(+) patients also received gentamicin (4% vs 0.1%; P < .001) and vancomycin more frequently (2.8% vs 0.7%; P < .001) compared to ADR(−) patients (Fig. 1). In total, 137 perioperative ADEs were identified, the most
common were skin eruption, documented in 59 cases (43%), allergic urticaria (N=10; 7.3%), and drug dermatitis (N=9; 6.6%). When cefazolin was administered, there was no difference in the perioperative ADE rate between penicillin ADR(+) allergy or hypersensitivity and ADR(−) patients (1.04% vs 0.75%, respectively; P=0.485). Overall, vancomycin was the antibiotic most commonly associated with a perioperative ADE, occurring in 3.3% of all cases. Penicillin ADR(+) patients experienced perioperative ADEs to vancomycin (9.7%), noncefazolin cepha- losporins (5.1%), and clindamycin (0.77%).
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