Antibiotics hypersensitivity reactions

Wills R, Henry RL, Francis JL. Antibiotic hypersensitivity reactions in cystic fibrosis. J Paediatr Child Health 1998 34(4) 325-9. 

As with all drugs, the specific side effects of the quinolones must be considered when they are chosen for treatment of bacterial infections [5]. Reactions of the gastrointestinal tract and the central neivous system are the most often observed adverse effects during therapy with quinolones. It should be underlined, however, that compared with many other antimicrobials, diarrhea is less frequently observed during quinolone treatment. Antibiotic-associated colitis has been observed rarely during quinolone therapy. Similarly, hypersensitivity reactions, as observed during therapy with penicillins and other (3-lactams, is less frequently caused by quinolones. Some other risks of quinolone therapy have been defined and must be considered if a drug from this class is chosen for treatment of bacterial infections. 

Discuss hypersensitivity reactions and pseudomembranous colitis as they relate to antibiotic therapy. 

Hypersensitivity reactions with P-lactam antibiotics, especially penicillin, may encompass any of the type I through IV Gell-Coombs classifications. The most common reactions are maculopapular and urticarial eruptions.7 While rare (less than 0.05%), anaphylaxis to penicillins causes the greatest concern because they are responsible for the majority of drug-induced anaphylaxis deaths in patients, accounting for 75% of all ana-i phylaxis cases in the United States.5,8 The treatment of ana-I phylaxis is given in Table 51-2.9... 

Monitor the patient for the development of potential complications of treatment such as delayed hypersensitivity reactions, antibiotic-induced diarrhea, pseudomembraneous colitis, or fungal superinfections (manifested as oral thrush). 

Acute drug-related hypersensitivity reactions (allergic responses) may cause tubulointerstitial nephritis, which will damage the tubules and interstitium. These reactions are most commonly observed with administration of methicillin and other synthetic antibiotics as well as furosemide and the thiazide diuretics. The onset of symptoms occurs in about 15 days. Symptoms include fever, eosinophilia, hematuria (blood in the urine), and proteinuria (proteins in the urine). Signs and symptoms of acute renal failure develop in about 50% of the cases. Discontinued use of the drug usually results in complete recovery however, some patients, especially the elderly, may experience permanent renal damage. 

Penicillin G 24 million units/24 h IV in four to six equally divided doses may be used in place of nafcillin or oxacillin if strain is penicillin susceptible (minimum inhibitory concentration 0,1 mcg/mL) and does not produce /5-lactamase vancomycin should be used in patients with immediate-type hypersensitivity reactions to beta-lactam antibiotics (see Table 37-3 for dosing guidelines) cefazolin may be substituted for nafcillin or oxacillin in patients with non-immediate-type hypersensitivity reactions to penicillins... 

Weiss, M.E. and Adkinson, N.F., Immediate hypersensitivity reactions to penicillin and related antibiotics, Clin. Allergy, 18, 515, 1988. 

Hypersensitivity reactions Make careful inquiry for a history of hypersensitivity reactions. Monitor patients who have had immediate hypersensitivity reactions to penicillins or cephalosporins. If an allergic reaction occurs, discontinue the drug and institute supportive treatment. Cross-sensitivity with other penicillins or -lactam antibiotics is rare. 

Pseudomembranous colitis Pseudomembranous colitis has been reported with nearly all antibacterial agents and may range in severity from mild to life-threatening. Hypersensitivity reactions Administer tigecycline with caution to patients with known hypersensitivity to tetracycline class antibiotics. 

Topical formulations of nystatin and of amphotericin B are useful in the management of Candida albicans infections of the skin. Both antibiotics are ineffective against dermatophytes. The use of nystatin is limited to topical treatment of cutaneous and mucosal Candida infections because of its narrow spectrum and its negligible absorption from the gastrointestinal tract. Hypersensitivity reactions are rare. It is not known whether topical nystatin can cause fetal harm when used by a pregnant woman. Amphotericin B has broader antifungal activity but its topical use is restricted to Candida. Topical use of amphotericin B has shown minimal absorption through the skin and is well tolerated. Limited human surveillance data do not indicate any harm to mother or fetus, but relative safety is still unknown. 

Because of potential toxicity, bacterial resistance, and the availability of many other effective alternatives, chloramphenicol is rarely used. It may be considered for treatment of serious rickettsial infections such as typhus and Rocky Mountain spotted fever. It is an alternative to a B-lactam antibiotic for treatment of meningococcal meningitis occurring in patients who have major hypersensitivity reactions to penicillin or bacterial meningitis caused by penicillin-resistant strains of pneumococci. The dosage is 50-100 mg/kg/d in four divided doses. 

The introduction of antibiotics into clinical medicine has brought about a whole range of unforeseen problems. Apart from potential toxicity and, with some antibiotics, such as penicillins, of hypersensitivity reactions, several micro-organisms (especially many types of bacteria) show high levels of resistance. Furthermore, transferability of resistance from resistant to sensitive cells of the same or different species or genus is a well-known phenomenon with potentially serious clinical consequences [6-8],... 

Dorzolamide is administered topically but can be absorbed systemically. Although there is risk of systemic hypersensitivity reactions to dorzolamide, a nonantibiotic sulfonamide, in patients allergic to sulfonamide antibiotics, the risk appears to be low. 

Steroids are specifically contraindicated in the treatment of HSV conjunctivitis, because they can increase virus replication and interfere with the host immune response to the infection. Topical antibiotics are also of limited value in treating HSV. The risk of bacterial superinfection is low, and the potential toxic and hypersensitivity reactions associated with topical antibiotic use may obscure the clinical course of the underlying viral infection. 

All routes of drug administration can affect ocular structures and functions. OADRs have been associated with topical ophthalmic administrations as well as local injections. Systemically, oral drug administration has been implicated most frequently in the development of OADRs. However, parenteral as well as inhaled or nasally applied drugs have also produced OADRs. Topical application to the skin, particularly if it is abraded or burned, may result in sufficient systemic absorption to lead to ocular side effects. Dermatologic use of antibiotics has resulted in ocular hypersensitivity reactions. 

Saxon A, Beall GN, Rohr AS, Adelman DC. Immediate hypersensitivity reactions to beta-lactam antibiotics. Ann Intern Med 1987 107 204—15... 

It is obvious that the development of new animal models, for example transgenic and knock-out mice, should create new possibilities for predicting the sensitizing potential of new antimicrobials. The sad fact that hypersensitivity reactions are among the most commonly occnrring adverse effects when antibiotics are nsed nnder-Unes the nrgent need for research efforts in academia and indnstry (227). 

Koch C, Hjelt K, Pedersen SS, Jensen ET, Jensen T, Lanng S, Valerius NH, Pedersen M, Hoiby N. Retrospective clinical study of hypersensitivity reactions to aztreonam and six other beta-lactam antibiotics in cystic fibrosis patients receiving multiple treatment courses. Rev Infect Dis 1991 13(Suppl 7) S608-11. 

Clavulanic acid has a very low immunogenic and allergenic potential in animals. The possible impact of its co-administration with other beta-lactam antibiotics is unknown (53). Two patients with IgE-mediated hypersensitivity to oral co-amoxiclav and positive skin tests for clavulanic acid, but not for penicillins, both tolerated oral amoxicillin. One patient was also challenged with clavulanic acid and developed urticaria, conjunctivitis, and bronchial obstruction (54). Since co-amoxiclav has been widely used since its introduction in 1981, the frequency of hypersensitivity reactions is low. The clinical data available on sulbactam and tazobactam are stiU hm-ited and do not allow an assessment of the frequency and pattern of associated hypersensitivity reactions (55). 

Imipenem, which is related to meropenem, has also been reported to cause toxic epidermal necrolysis (34). The authors stated that to the best of their knowledge, this was the first report of a possible cross-reaction between two classes of antibiotics in causing toxic epidermal necrolysis. The time between first administration and the occurrence of epidermal necrolysis is considerably shorter in recurrence or provocation testing (35,36). They also claimed that it is likely that the beta-lactam ring is responsible for this hypersensitivity reaction, citing the evidence that the patient had been given amoxicillin 15 days before the cephalosporin, and that could have served as the sensitizing event. They did not discuss whether aztreonam, a monobactam, also could have caused a cross-reaction however, it has been involved in two cases of fatal toxic epidermal necrolysis (37). 

---