develop a rash, yet others report the reaction to a penicillin antibiotic was limited to a
maculopapular rash. Responses to any of these indicate that if the patient had a reaction to
penicillin, it was of the non-anaphylactoid variety. Patients with drug fever or rash due to
penicillins may be safely given penicillins again (12,13). Reactions tob-lactams are stereotyped
such that if the patient had a fever as the manifestation of penicillin allergy, on re-challenge,
the patient will develop fever again as opposed to another clinical manifestation of penicillin
allergy. Patients with drug fevers or drug rashes due to penicillins, at worst, will only have a
similar non-anaphylactic reaction upon re-challenge with penicillin. Alternately, they may
have no reaction at all if theb-lactam chosen is sufficiently different antigenetically than the
one initially causing the reaction. It is not uncommon in clinical practice with third-generation
cephalosporin allergies to have patients not react to cefoperazone, which is the most
antigenemic member of third-generations cephalosporins. Among the second-generation
cephalosporins, cefoxitin is the least likely to cross-react with other second-generation
cephalosporins (12–14).
CROSS REACTIONS BETWEEN PENICILLINS ANDb-LACTAMS
When cephalosporins were first introduced, the reported cross-reactivity rate with penicillins
was high as 30%. Subsequently, actual cross allergic reactions were<3%. Many of the cross-
reactions initially reported between penicillins and cephalosporins were nonspecific allergic
reactions not based on penicillin/cephalosporin cross-reactivity. Patients with a penicillin
allergy who have had a non-anaphylactic reaction may safely be given ab-lactam antibiotic. In
the unlikely event the patient has a reaction, the patient would develop a drug fever or rash,
but not anaphylaxis. Theb-lactam class of drugs includes the penicillins, the semi-synthetic
penicillins, the modified penicillins, the amino-penicillins, and the ureido-penicillins (15–22).
CARBAPENEMS AND MONOBACTAMS
From an allergic perspective b-lactams may be divided into carbapenems and non-
carbapenems. Among the non-carbapenems are first-, second-, third-, and fourth-generation
cephalosporins. Allergy to one is likely to result in cross-reactivity with another with the
exceptions of cefoxitin among the second-generation cephalosporins, and cefoperazone among
the third-generation cephalosporins. Although carbapenems are structurally related tob-
lactam antibiotics from an allergic perspective, they should not be regarded asb-lactam
antibiotics. Carbapenems, e.g., meropenem, do not react with otherb-lactams or penicillin-
derivatives. Therefore, carbapenems are frequently used as an alternative class of antibiotics to
b-lactams and do not cross-react with any penicillin orb-lactam to such an extent that the
reaction would be reportable in the literature. Carbapenems in general, and meropenem in
particular is completely safe to give patients with known/suspected history of penicillin
anaphylaxis. The more likely the history of anaphylaxis to penicillin, the more confidently can
the clinician safely use meropenem (23–25).
NONb-LACTAM ANTIBIOTICS IN PATIENTS WITH PENICILLIN
ANAPHYLACTIC REACTIONS
In patients giving a history of an anaphylactic reaction, i.e., anaphylaxis, laryngospasm,
bronchospasm, hypotension, or total body hives, it is important to select a nonb-lactam
antibiotic to avoid complicating the already serious situation in the critical care setting. As with
non-anaphylactoid penicillin reactions, anaphylactic reactions tend to be stereotyped with
repeated exposures. Patients who develop laryngospasm as the manifestation of their
penicillin allergy do not develop total body hives on subsequent re-exposure but will
repeatedly develop laryngospasm as the main manifestation of their anaphylactic reaction. As
with other manifestations of anaphylaxis, the reactions are stereotyped and will be repetitive
and not change to another anaphylactoid manifestation. Fortunately there are so many highly
effective nonb-lactam antibiotics available at the present time, that invariably there are many
appropriate nonb-lactam antibiotics to choose from to treat the life-threatening infections
encountered in the CCU (Table 1) (22–25).
Antibiotic classes that have no allergic cross-reactivity withb-lactams include the
macrolides, tetracyclines, clindamycin, chloramphenicol, TMP/SMX, aminoglycosides,
Antibiotic Therapy in the Penicillin Allergic Patient in Critical Care 537