Adverse Reactions Associated with Penicillins, Carbapenems, Monobactams, and Clindamycin: A Retrospective Population-based Study

Abstract

Background: Limited population-based data on penicillin-, carbapenem-, monobactam-, and clindamycin-associated reported adverse reactions exist.

Objective: To collect data on penicillin, carbapenem, monobactam, and clindamycin usage and associated adverse reactions.

Methods: Data from January 1, 2009, to December 31, 2017, in Kaiser Permanente Southern California were collected.

Results: There were 6,144,422 unique individuals, mean age 33.6 ± 21.1 years, 52.2% females, with at least 1 health care visit during the 9-year study interval, for a total of 37,387,313 patient-years of follow-up. This population was exposed to 5,617,402 courses of oral penicillins, 370,478 courses of parenteral penicillins, 59,645 courses of parenteral carbapenems or monobactams, 817,232 courses of oral clindamycin, and 215,880 courses of parenteral clindamycin. New penicillin allergies were reported more commonly after parenteral (0.85%) compared with oral (0.74%) exposures (P < .0001). There were 22 cases (1 in 255,320) of oral penicillin-associated anaphylaxis and 3 cases (1 in 123,792) of parenteral penicillin-associated anaphylaxis (P < .001). There were 2 clindamycin-associated anaphylaxis cases, 1 (1 in 817,232) oral and 1 (1 in 215,880) parenteral. There were 2 (1 in 2,993,940) penicillin-associated serious cutaneous adverse reaction (SCAR) cases, but both also had co-trimoxazole coexposure within 45 days. There was 1 (1 in 1,033,112) clindamycin-associated SCAR. Clostridioides difficile infection was more common after parenteral exposures, and with extended-spectrum penicillins, beta-lactamase combinations, carbapenems, monobactam, and clindamycin exposures compared with oral penicillins or clindamycin.

Conclusions: Only 1 of 1543 (0.065%) oral and 1 of 1030 (0.097%) parenteral penicillin-associated allergy reports were confirmed to be anaphylaxis. C. difficile was more common after parenteral versus oral penicillin, carbapenem, monobactam, and clindamycin exposures, and with broader spectrum antibiotic exposures.

Keywords: Adverse drug reaction; Allergy; Anaphylaxis; Beta-lactam; Carbapenem; Clindamycin; Epidemiology; Hypersensitivity; Infection; Monobactam; Oral; Parenteral; Penicillin; Serious cutaneous adverse reaction.