ANAPHYLAXIS
Anaphylaxis is an acute hypersensitivity reaction that can result in immediate urticaria,
laryngospasm, bronchospasm, hypotension, and death. In the critical care setting, these
reactions may be masked by underlying conditions or other therapies. While anaphylaxis can
be precipitated by antigen–antibody complexes, it is usually IgE mediated. The binding of
antibiotic epitopes to specific preformed IgE antibodies on the surface of mast cells results in
the release of histamine and other mediators that lead to the aforementioned clinical
presentations. b-Lactams are more often associated with these reactions than other
antimicrobials. Best data exist for penicillin, where the risk of anaphylaxis is about 0.01%
(8). Death occurs in one of every 100,000 courses of this agent (9). Conversely, only 10% to
20% of patients who claim to have an allergy to penicillin are truly allergic as determined by
skin testing (10). Fifty percent of patients with a positive skin test will have an immediate
reaction when challenged with penicillins (11). Approximately 4% of patients with a history
of penicillin allergy who test positive to penicillin will experience a reaction (only rarely
anaphylaxis) when given a cephalosporin (12). First-generation cephalosporins and
cefamandole share a side chain similar to the chain present in penicillin and amoxicillin,
and there is an increased risk of allergic reactions to these cephalosporins in penicillin-
allergic patients. Other second-generation and third-generation cephalosporins have differ-
ent side chains than penicillin and amoxicillin; a recent meta-analysis found no increased risk
of allergic reactions to these cephalosporinsin penicillin-allergic patients when compared
with patients without a penicillin allergy (13). While early studies concluded that there is an
increased risk of reactions inpenicillin-allergic patients given carbapenems, recent studies
have demonstrated that administering meropenem and imipenem to these patients is safe
(14–17). Aztreonam can be given safely to patients with a history of anaphylaxis to all
b-lactams except ceftazidime (9).
CARDIOTOXICITY
A survey of intensivists at our institution found that the antibiotic adverse reaction that
concerns them the most is QT prolongation with ventricular arrhythmia. In patients with
susceptible substrate (e.g., coronary artery disease), precipitators (e.g., drugs and/or
electrolyte disturbances) can cause torsades des pointes and sudden death (18). Often, QT
prolongation precedes the drug-induced arrhythmia. However, drug-induced QT prolonga-
tion does not always result in torsades des pointes nor do medications that can cause torsades
always prolong the QT interval. Antibiotics that can prolong the QT interval include
macrolides, fluoroquinolones, azoles, pentamidine, and quinine. A cohort study of patients
receiving oral erythromycin found a two-fold increased risk of sudden death in patients
receiving this macrolide (19). Combining antibiotics and other drugs (e.g., amiodarone,
haloperidol, diltiazem) that prolong the QT interval can increase the risk of torsades des
pointes and sudden death (18). To avoid prescribing multiple medications that prolong the QT
interval and predispose patients to torsades des pointes, intensivists and pharmacists can look
up http://www.azcert.org. Clinicians should consider using alternative antibiotics in patients with a
baseline QTc interval>500 milliseconds. If the QTc interval increases by 30 to 60 milliseconds
or to more than 500 milliseconds, replacing known offending agent(s) with a different drug
should be considered (18).
Myocardial depression, hypotension, and sudden death have been reported with
vancomycin use, generally in the setting of rapid administration in the perioperative period
(20,21). Similarly, rapid administration of amphotericin B has been associated with ventricular
fibrillation and asystole, especially in patients with renal dysfunction (22). Amphotericins and
pentamidine infusions can precipitate hypotension.
NEPHROTOXICITY
Acute renal failure is common in ICU patients and associated with a risk of mortality of>60%
(23). Numerous agents used in the ICU are capable of affecting renal function. Mechanisms
include decreased glomerular filtration, acute tubular necrosis, interstitial nephritis, and
crystallization of the drug within the tubules. With regard to antibiotics, the aminoglycosides
544 Granowitz and Brown