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Review

Allergy Asthma Immunol Res. 2010 April;2(2):77-86. doi: 10.4168/aair.2010.2.2.77 pISSN 2092-7355 • eISSN 2092-7363

Update on the Management of Antibiotic Allergy
Bernard Yu-Hor Thong*
Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Drug allergy to antibiotics may occur in the form of immediate or non-immediate (delayed) hypersensitivity reactions. Immediate reactions are usually IgE-mediated whereas non-immediate hypersensitivity reactions are usually non-IgE or T-cell mediated. The clinical manifestations of antibiotic allergy may be cutaneous, organ-specific (e.g., blood dyscracias, hepatitis, interstitial nephritis), systemic (e.g., anaphylaxis, drug induced hypersensitivity syndrome) or various combinations of these. Severe cutaneous adverse reactions manifesting as Stevens Johnson syndrome or toxic epidermal necrolysis (TEN) may be potentially life-threatening. The management of antibiotic allergy begins with the identification of the putative antibiotic from a detailed and accurate drug history, complemented by validated in-vivo and in-vitro allergological tests. This will facilitate avoidance of the putative antibiotic through patient education, use of drug alert cards, and electronic medical records with in-built drug allergy/adverse drug reaction prescription and dispensing checks. Knowledge of the evidence for specific antibiotic cross-reactivities is also important in patient education. Apart from withdrawal of the putative antibiotic, immunomodulatory agents like high-dose intravenous immunoglobulins may have a role in TEN. Drug desensitization where the benefits outweigh the risks, and where no alternative antibiotics can be used for various reasons, may be considered in certain situations. Allergological issues pertaining to electronic drug allergy alerts, computerized physician prescriptions and decision support systems, and antibiotic de-escalation in antimicrobial stewardship programmes are also discussed. Key Words: Anaphylaxis; desensitization; drug hypersensitivity; Stevens Johnson syndrome; toxic epidermal necrolysis

INTRODUCTION
Antibiotics are one of the most common causes of drug allergy in most epidemiological studies, both among adults and children.1-6 Among the various classes of antibiotics, beta-lactam antibiotics (penicillins and cephalosporins), cotrimoxazole and quinolones are some of the most common causes of antibiotic allergy. Antibiotic allergy may occur in the form of immediate or nonimmediate (delayed) hypersensitivity reactions. Immediate reactions are usually IgE-mediated whereas non-immediate hypersensitivity reactions are usually non-IgE or T-cell mediated.7 The clinical manifestations of antibiotic allergy may be cutaneous, organ-specific (e.g., blood dyscracias, hepatitis, interstitial nephritis), systemic (e.g., anaphylaxis, drug induced hypersensitivity syndrome) or various combinations of these. Severe cutaneous adverse reactions (SCAR) manifesting as Stevens Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) may be potentially life-threatening.8

cation of the putative antibiotic from a detailed and accurate drug history.9 Not infrequently, the drug history may need to be obtained from a combination of sources other than the patient, including care-givers, records from other prescribing physicians and both non-electronic and electronic medical records.10 With the use of digital photography, instructing patients to take digital photographs of the initial rash may become increasingly important in helping the allergist to diagnose a drug eruption, especially when the rash is likely to have resolved by the time the patient sees the allergist.11-13 In the diagnosis of immediate allergic reactions to antibiotics, the in-vivo tests available are skin prick tests (SPT) and intradermal tests (IDT).14,15 However, these have been well validated mainly for beta-lactam antibiotics and less so for other classes of antibiotics. For in-vitro tests, commercially available assays include fluorescent enzyme immunoassays (FEIA) (ImmunoCorrespondence to: Bernard Yu-Hor Thong, MBBS, MRCP (UK), Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore. Tel: +65-6357-7822; Fax: +65-6357-7837; E-mail: bernard_thong@ttsh.com.sg Received: October 18, 2009; Accepted: October 19, 2009.
•There are no financial or other issues that might lead to conflict of interest.

DIAGNOSIS OF ANTIBIOTIC ALLERGY
The management of antibiotic allergy begins with the identifi-

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quinolones. anxious people who would refuse to take the recommended drug without proof of tolerance • to exclude cross-reactivity of related drugs in proven hypersensitivity.Thong CAP®. eczema.. ampicillin). vagal symptoms following the use of an antibiotic • to provide safe pharmacologically and/or structurally nonrelated drugs in proven hypersensitivity e. Baboon’s syndrome). isoniazid. metronidazole. or when alternative drugs are more expensive). Recent studies of in vitro rapid antigen desensitizations implicate mast cells and basophils as cellular targets. slow desensitization results in patients achieving the total target dose within a few days to weeks.g. but rarely positive in TEN. TREATMENT OF ANTIBIOTIC ALLERGY Definitive treatment involves cessation of the suspected antibiotic. sulfonamides. minocycline.4168/aair. the sensitivity of the test is usually drug. up-regulation of cell surface activation markers (e. and also because non-immediate reactions are generally more common than Volume 2. meropenam. mostly in Europe. DPT can generally be carried out safely with careful patient selection.g..2(2):77-86. April 2010 immediate reactions in clinical practice. cefotaxime). 78 http://e-aair. imipenam. Desensitization is a method of reintroducing antibiotics into highly sensitized patients to induce tolerance. However.28 Blinded (single. Like the patch test. LTT are often positive in MPE. Desensitization should be avoided should the initial reaction be potentially life-threatening reactions like immunobullous eruptions and SJS/TEN. symmetric drug-related intertriginous and flexural exanthema (SDRIFE.21 This test can be technically difficult to carry out and are thus often done in specialized centres. the LTT is usually positive in a drug. day 4. e. fixed drug eruptions (FDE) (when done on the lesional skin). MPE during aminopenicillin treatment with negative allergological tests. CD69). It is occasionally positive in hepatitis and nephritis. Similar to patch tests.18 For non-immediate reactions.2. infection with multiresistant organisms. In certain instances where the antibiotic is required because there are no better alternatives (e.19 In-vivo tests available for non-immediate reactions include the lymphocyte transformation test (LTT) which is a proliferation assay which detects drug-specific T-cells.or double-blind placebo-control) challenges may sometimes be needed in patients with nonsuggestive history and non-specific symptoms. Phadia) which are less sensitive and specific compared to skin tests. clarithromycin. RAST) have over the years been replaced with the FEIA assays. as well as syk.22 Novel in-vitro tests evaluating cytokine secretion. clindamycin. metronidazole. and drug rash with eosinophilia and systemic symptoms (DRESS).29 Rapid desensitization results in patients achieving the target total dose of the drug through rapidly escalating doses usually within 24 hours. Radioimmunoassays previously used mainly for the diagnosis of penicillin allergy (including the radioallergosorbent test. Patch tests have been described in the diagnosis of non-immediate reactions to amoxicillin.16. Number 2. e.g. streptomycin. with the exception of anaphylaxis. cotrimoxazole. Patch tests are often done in Europe to assist in the diagnosis of non-immediate reactions to various antibiotics. a signal transducing molecule.and reaction-specific manner. these tests are available mainly for penicillins and cephalosporins. AGEP. rifamipicin. and signal transducer and activator of transcription 6 (STAT6). cytopaenias and vasculitis. rifampicin. doi: 10. e. erythromycin. drug provocation tests (DPT) often have to used in the diagnostic evaluation of drug allergy.23-27 The indications for DPT are as follows:23 • to exclude hypersensitivity in non-suggestive history of drug hypersensitivity and in patients with non-specific symptoms. and analysis of cytotoxic potential (granzyme B. cefcapene pivoxil. ciprofloxacin. Again. Sweden). cotrimoxazole. isoniazid and rifampicin.17 Flow-cytometric based basophil activation tests (BAT) (flow assay stimulation test. non-conclusive or non-available allergologic tests. Various desensitization protocols are available for penicillin (benzylpenicillin. vancomycin and fluoroquinolones. Buhlmann Laboratories) which measure CD69 or CD203c on drug-specific activated basophils may have a role in the diagnosis of antibiotic allergy.19 Delayed reactions are considered positive when there is an infiltrated erythematous reaction. The tests are read on day 2. FAST/FlowCAST®.2. spiramycin.g. However such individuals are still considered as being allergic to the antibiotic. pristinamycin.g. but have not been shown to be very useful in SJS/ TEN and vasculitis.org Allergy Asthma Immunol Res.and reactionspecific. acute generalized exanthematous pustulosis (AGEP). tetracycline. delayed readings of IDT are done at 24 hours and 72 hours. a cephalosporin in a penicillin-allergic subject • to establish a firm diagnosis in suggestive history of drug hypersensitivity with negative. 2010 April. cephalosporins (ceftazidime. ethambutol.20 The patch test allergens can be prepared in-house or using commercially available products (Chemotechnique Diagnostics®.g. teicoplanin and vancomycin. drug desensitization can be carried out. Antibiotics which have been found to often test positive in LTT are beta-lactams. isoniazid.22 In view of the limited number of in-vivo and in-vitro tests commercially available for most antibiotics. and the vehicle used is usually petrolatum.2010. doxycycline. other antibiotics in beta lactam-allergic patients. and day 7 (if negative on days 2 and 4). with studies so far mainly focused on beta-lactam allergy. Patch tests are generally useful in maculopapular exanthema (MPE).21. CD107) remain as research tools. fluoroquinolones. which is responsible for the transcription of interleukin (IL)-4 and IL-13.77 . macrolides. bullous exanthema.

Non-immediate reactions range from mild MPE and FDE to serious SJS and TEN. specific IgE assays.36 depending on when the sample was taken from the time of the initial clinical reaction. with the FEIA currently being the most widely commercially available test. In September 2009. the sensitivity (42-74%) and specificity (85-100%) reported varied among studies. MDM and/or amoxicillin in the respective studies.39 Using a combination of skin tests.42 Cephalosporin allergy The reported cross-reactivity for IgE-mediated hypersensitivity between cephalosporins and penicillins in patients with Ig-E COTRIMOXAZOLE ALLERGY Cotrimoxazole is an immunogenic drug which may cause both immediate and non-immediate reactions. this may the reason why the penicillin allergic individuals appear to be able to tolerate most third and fourth generation cephalosporins. should be carried out with benzylpenicillin.43. hence a positive test is useful in confirming beta lactam allergy but a negative test does not rule it out. and thus could result in potentially positive drug provocation tests being done.48 Similarly. but rarely positive (<10%) in blood dyscracias and TEN associated with drug allergy.31 In 2004. followed by cellular tests in negative patients.5% based on patients with cell-mediated allergy to penicillins showing positive patch tests to at least one penicillin reagent and imipenem-cilastatin. Allergopharma and Hollister-Stier announced their decision to stop the commercial production of penicillin reagents (Allergopen® and PrePen® respectively). shared by penicillins and cephalosporins.37. LTT for beta lactam allergy has a low sensitivity of 60-70%. this may miss patients who may have tested positive to PPL or MDM. cephalothin and cephaloridine. and specificity of 93%.41 Patch tests when used.38 Carbapenem allergy Earlier studies from the late 1980s showed that cross-reactivity between penicillin and imipenem allergy was 50% based on 10 of 20 patients with penicillin allergy being skin test positive to one or more penicillin or imipenem determinants.49 Recent prospective studies in adults and children with penicillin (predominantly amoxicillin) IgE-mediated allergy have shown that the cross-reactivity based on positive skin tests to imipenamcilastatin50 and meropenam51. The LTT is often positive in AGEP and DRESS. and that patients who were SPT/IDT negative to imipenam-cilastatin and meropenam were able to tolerate a graded.30.AAIR Management of Antibiotic Allergy mediated penicillin allergy of 5-10%.52 was 0. seems to play a dominant role in determining the specificity of immunologic reactions to cephalosporins. penicillin can be administered safely to patients allergic to cephalosporins and with a negative skin test result to penicillin determinants.4168/aair.2010.56 Slow acetylator phenotype and genotype.14 The R1 side chain rather than the betalactam structure. For delayed reactions to carbapenams. minor determinant mix (MDM) and benzylpenicillin G or amoxicillin have been validated in various studies and shown to be useful in the evaluation of suspected immediate reactions to penicillin. This is especially prevalent in HIV-infected individuals where cotrimoxazole is used for the treatment and prophylaxis for Pneumocystis jiroveci infection and toxoplasmosis. ampicillin. when used in the diagnosis of beta-lactam allergy.44 In addition. the cross-reactivity with penicillins was 5.33 and is presently used in many countries worldwide.58 and major histocompatibility complex (MHC) polymorphisms59 have not been shown to be major predisposing risk factors for cotrimoxazole hypersensi- Allergy Asthma Immunol Res. 2010 April. Pre-Pen® was approved for marketing by the Food and Drug Administration (FDA) through ALK-Abello and Allerquest LLC. and the outcomes of skin tests to PPL. All patients with negative patch test and delayed IDT reading to imipenamcilastatin tolerated an intramuscular provocation test.35. The determinants used in FEIA are benzylpenicilloyl and amoxicilloyl. However.org 79 .2.53 BETA-LACTAM ALLERGY Penicillin allergy Allergic reactions to beta-lactam antibiotics are the most common cause of drug allergies in most epidemiological studies on adverse drug reactions. doi: 10.27 this is recommended by the British Society of Allergy and Clinical Immunology (BSACI)46 and the European Academy of Allergy and Clinical Immunology (EAACI). The flow cytometric BAT assay. and any suspect penicillins and/ or cephalosporins. amoxicillin.34 However. In countries where commercial PPL and MDM are not available.45 Although the practice parameters of the AAAAI in 1999 did not advocate the use of cephalosporin skin testing.38 However. A Spanish product (Diater®) was subsequently found to be a reliable and consistent alternative32.57.9%. SPT and IDT using commercially available penicilloyl polylysine (PPL). can facilitate confirmation of betalactam allergy.54. the test is unable to differentiate between selective reactors and cross-reactors. were based on early studies from the 1970s on patients with a history of penicillin allergy who developed allergic reactions to cephalexin. has a sensitivity of 50%. The flow cytometric BAT assay appears to be a promising invitro test in the diagnosis of cephalosporin allergy as well as penicillin allergy. early cephalosporin antibiotics contained traces of penicillin.47 Thus. In-vitro tests are often less sensitive and more expensive when compared to skin tests. challenge dose of intravenous imipenam-cilastatin and meropenam respectively.55 and are more common than immediate reactions. skin testing with benzylpenicillin may be used in lieu.77 http://e-aair. and tests become negative the longer the duration from the initial reaction.2(2):77-86. avoiding DPT in up to two-thirds of patients.2.40 Using an alternative marker like CD203c may increase the sensitivity of these tests.37.

77 .84. patch tests and oral challenges if skin tests are negative.91-95 there have also been reports of patients with teicoplanin who tolerated vancomycin. subepidermal.65 Thus.68 TETRACYCLINE ALLERGY Minocycline can cause serious adverse reactions including drug hypersensitivity syndrome. which is commonly associated with too rapid an infusion of vancomycin resulting in direct mast cell histamine release.org Allergy Asthma Immunol Res. in particular drug allergies to doxycycline and tetracycline are relatively rare. adverse drug reactions. TUBERCULOUS DRUG ALLERGY Mycobacterium tuberculosis (MTC) infection remains endemic in certain parts of Asia.72 Apart from exanthematous eruptions.69 Apart from photodermatoses and photo-onycholysis which are usually phototoxic in nature.80-83 Linear IgA bullous dermatosis (LABD) is an autoimmune.60 Volume 2. patients with allergy to a fluoroquinolone should avoid other fluoroquinolones. Teicoplanin.74 The use of a combination of skin prick tests.78 FLUOROQUINOLONE ALLERGY Fluoroquinolone allergy may present in the form of immediate and non-immediate reactions. with non-IgE mediated reactions occurring after the first dose with no previous history of sensitization. Non-immediate reactions are much more common than immediate reactions to 80 http://e-aair. Immediate reactions [anaphylaxis86. Rapid and slow desensitization to cotrimoxazole especially in the setting of HIV infection. Allergic reactions to macrolide antibiotics appear to be relatively uncommon (0.62 and delayed reactions through generation and analysis (flow cytometry and proliferation assays) of quinolone-specific T cell clones respectively. This is in contrast to vancomycin red man syndrome. Successful desensitization has also been reported.79 Anaphylaxis from vancomycin may be through IgE mediated allergic mechanisms or non-IgE mediated non-allergic mechanisms.2. These occur on average within 4 weeks of therapy.70 CLINDAMYCIN ALLERGY Clindamycin may be associated with both immediate and non-immediate allergic reactions. April 2010 AGEP73 and TEN.97 Pre-operative allergy clinic assessment together with penicillin skin testing has been shown to be an effective intervention in reducing unnecessary use of prophylactic vancomycin perioperatively. midecamycin) macrolides. appear to be more useful compared to SPT and IDT alone as negative skin tests may still result in positive challenges.85 Lesions typically appear during vancomycin therapy. Although there have been reports of cross-reactivity between individuals with vancomycin and teicoplanin allergy.2(2):77-86. toxic epidermal necrolysis and leukocytoclastic vasculitis have been reported.4% to 3% of treatments).62 Although previous studies had shown that skin tests to quinolones lack sensitivity and specificity. vesiculobullous disease that has been commonly associated with the use of vancomycin. another glycopeptide. cases reported in the literature include contact dermatitis.61. Number 2.87] and non-immediate reactions [rash. in children and adults. rifampicin.98. MACROLIDE ALLERGY Macrolides are classified according to the number of carbon atoms in the chemical structure: 14 membered (erythromicin.96.Thong tivity in HIV-infected individuals. doi: 10. has rarely been reported to be associated with allergic drug reactions including exfoliative dermatitis and maculopapular rash. The immediate reactions may be IgE mediated or non IgE mediated. has fewer side effects compared to vancomycin. showing linear IgA and C3 deposits at the basement membrane zone on direct immunofluorescence. 15 membered (azithromycin) and 16 membered (spiramycin. whereas minocycline-induced lupus occurs on average 2 years after the initiation of therapy.99 This would be helpful in the long-term in reducing the spread of vancomycin resistant infections in hospitals and within the community.67 and non-immediate reactions like fixed drug eruptions.2010. roxithromycin. 2010 April. dirithromycin. Various effective desensitization regimes have been described in the treatment of vancomycin anaphylaxis.4168/aair.76 Clindamycin desensitization has been reported in the literature in particular in HIV-infected individuals. josamycin.2. ethambutol and pyrazinamide.88 AGEP89 and DHS90] are infrequent. serum sickness and drug-induced lupus. Histopathologic examination and immunofluorescence studies are diagnostic. Withdrawal of vancomycin is all that is required.63 a negative skin test could predict a negative challenge test in 94% of the challenged cases. clarithromycin).75.71 However.64 Cross-reactivity has been demonstrated for immediate reactions through positive skin tests to a range of quinolones. and the need for potentially expensive antibiotics like linezolid and tigecycline. the prevalence of such reactions is rare. 24 hours to 15 days after the first dose.77. for clarithromycin and azithromycin. has been shown to be effective and safe.66 Cases of immediate reactions in the form of anaphylaxis.79 Red man syndrome is very unusual with teicoplanin because this compound does not cause histamine release even at faster infusion rates than those of vancomycin. VANCOMYCIN AND TEICOPLANIN ALLERGY Vancomycin. a glycopeptide. Treatment of MTC infections involves combinations of anti-tuberculous drugs including isoniazid.

because leaving patients on anti-tuberculous monotherapy would increase the risk of emergence of drug-resistant tuberculosis.. systemic corticosteroids (0. the use of systemic corticosteroids has been supported by case reports and series (prospective and retrospective) which showed positive outcomes with the early use of corticosteroids (prednisolone 1 mg/kg/day or methylprednisolone 1-2 mg/kg/day) within 72 hours was beneficial in arresting the pro- Allergy Asthma Immunol Res. macrolides). The risks of desensitization need to be explained carefully to the patient provided combinations of second-line anti-tuberculous drugs (e.112 In DHS. there were also other studies which showed harm or no benefit. different brands of IVIg used with different dosing regimens. The most common long-term sequelae is sicca syndrome. Diagnosis using LTT have not been useful to date. In SJS. followed by antibiotic drugs (in descending order of frequency: cephalosporins. Although there were wide variation in patients and treatment protocols.107-111 These regimes often involve reintroducing the anti-tuberculous drugs as soon as the allergic reaction has settled. quinolones.AAIR anti-tuberculous drugs. High-dose IVIg did not appear to reduce the severity of visually significant ocular complications. DHS. Others include corneal ulceration.103 have all been reported in the literature. and fornix sweeping.83 g/day in the treatment of TEN. HLA B*38 showed only a weak association with sulfamethoxazole induced SJS/TEN54 in contrast to antiepileptic drugs and allopurinol where HLA associations are stronger and ethnically related.126 Other therapies like cyclophosphamide127 and plasmapharesis128 have not been shown to be useful. however. and hence the effectiveness of systemic corticosteroids. and long-term sequelae from 1% to 50%. desensitization would need to be considered very carefully in consultation with the attending infectious diseases physician or pulmonologist. Drug eruptions100 in the form of MPE and lichenoid drug eruptions.. Management of Antibiotic Allergy gression of SJS.20 In practice.8 In the study of Roujeau et al. Combination therapy also arrested progression earlier and decreased the hospitalization time. with at most a 3-5 day interval apart. aminopenicillins. SJS/TEN102. The decrease in the mortality rate. In early TEN. 2010 April.g. meaning that the total dose of corti- SEVERE CUTANEOUS ADVERSE REACTIONS (SCAR) Severe cutaneous adverse reactions (SCAR) include SJS.101 haematological reactions.5 to 1 mg/kg/day) tapered over 6-8 weeks rapidly improves symptoms and laboratory measurements.4168/aair. If the initial allergic reaction was SJS/TEN. valproic acid. In the last decade. hepatitis. human herpes virus 6. of duration of up to 3 weeks in case series of patients with severe TEN suggest that the risks of infection outweighed the benefits. Relapses of rash and hepatitis may occur as corticosteroids are tapered. between 10-30% of epidermal detachment occurs which can sometimes be diagnosed clinically from a positive Nikolsky’s sign or histological evidence of epidermal necrolysis. topical corticosteroids. are standard of care for which there are no controlled trials.113 Sequential reactivation of herpes viruses (e. and lamotrigine). the overall mortality rate was around 20% with earlier re-epithelialization demonstrated in some of the studies. The rationale for the use of IVIg is based on the inhibition of Fas-mediated keratinocyte apoptosis in TEN by naturally occurring Fas-blocking antibodies within the IVIg. which in the end may not be helpful.org 81 . phenytoin.122 Systemic corticosteroids should not been used as most series have suggested that the risks outweigh the benefits. Treatment modalities for ocular complications include topical antibiotics. it is often not clinically feasible to leave MTC infection untreated for 6 weeks pending evaluation using LTT or patch tests. was not statistically significant. tetracyclines. cycloserine) are not an option.121 TEN is defined as the detachment of the epidermis affecting more than 30% body surface area of skin involvement. doi: 10. carbamazepine. then nonsteriodal anti-inflammatory drugs (especially oxicam) and allopurinol.2010. but its impact on the long term disease course is not known.135 Significant dry eye problems and photophobia may also be avoided with this intervention.. Controlled clinical trials are lacking on the use of systemic corticosteroids in DHS. The prevalence of acute ocular complications ranges from 6% to 100%.19.2(2):77-86.2. corneal epithelial defect. anticonvulsants (phenobarbital.123-125 The only doubleblind placebo-controlled trial to date in the management of TEN.54 sulfonamides were the most strongly associated with TEN. quinolones. Ebstein Barr virus. early referral to a specialized unit. A recent retrospective study from China suggested that combination therapy with corticosteroid and high dose IVIG exhibited a tendency to reduce the mortality rate in comparison with administration of corticosteroid alone. dapsone. more than one drug often needs to be reintroduced. supportive measures including specialized nursing. The use of oral and intravenous cyclosporine 3-5 mg/kg/day. cytomegalovirus)114 and subsequent triggering of autoimmunity115 may explain these relapses. symblepharon and fornix foreshortening.77 http://e-aair. skin care including the use of Biobrane dressings.116-120 However.134 Early intervention with cryopreserved amniotic membrane transplantation was shown in a recent study to suppress inflammation and promote epithelial healing at the acute stage. In addition. TEN and DHS or DRESS).2.g. As such. Apart from prompt withdrawal of the suspected drug. rapid oral desensitization regimes have been described for isoniazid. lubricants. nutritional and respiratory care and support. imidazole antifungals. rifampicin and ethambutol.104-106 Patch tests are also not consistently useful as they are dependent on the type of cutaneous drug eruption. several case series129-133 have described the use of high dose intravenous immunoglobulins (IVIg) from 0. using thalidomide was stopped because there was excessive mortality in the thalidomide group.

Jick H. DRUG-INDUCED LUPUS Drug-induced lupus erythematosus (DILE) is defined as a lupus-like syndrome temporally related to continuous drug exposure which resolves after discontinuation of the offending drug. Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization. Lanier BQ. clinical pharmacists.136 Volume 2. McCaig LF.256: 3358-63. visceral involvement. Bigby M. meropenam). Stern RS. Thong BY. a 20-year survey. 273:214-9. In most cases of classic DILE. Cars O. Ann Allergy Asthma Immunol 2003. low serum complement levels as well as anti-extractable nuclear antigen antibodies and anti-dsDNA antibodies are rarely present. should be avoided in the presence of on-going sepsis unless no other alternative antibiotics are available. in the patient with a high probability of allergy to a narrow spectrum antibiotic (e. 2010 April. and review of antimicrobial prescribing with feedback to prescribers. clinical microbiologists. Bieber T. Platts-Mills TA.Thong costeroid may be reduced. CONCLUSIONS Antibiotics may cause various types of allergic drug reactions ranging from mild to serious cutaneous reactions. Motala C. it would be prudent to continue the broad-spectrum antibiotic rather than to consider REFERENCES 1. Williams HC. Drug desensitization may be considered in cases where the risks of retrying the drug outweigh the benefits. Arndt K. Allergy 1997. Leong KP. 7. 82 http://e-aair. April 2010 skin testing and desensitization to penicillin G in the presence of on-going sepsis where alternative antibiotic choices remain available. penicillin G) who has been tolerating a broadspectrum antibiotic (e. In contrast. Dahl R.2010. J Allergy Clin Immunol 2004. organ-specific or systemic reactions. did not lead to earlier tapering of corticosteroid.2(2):77-86. using such electronic alerts in any type of electronic medication record system as a decision support tool to facilitate antibiotic prescribing has to be done very cautiously. Zehnder D. Variation in antibiotic use in the European Union. these are present in half the cases of anti-tumour necrosis factor (TNF) alpha inhibitor induced DILE. 4. ANTIBIOTIC ALLERGY AND ANTIMICROBIAL STEWARDSHIP PROGRAMMES Antimicrobial stewardship programs in hospitals seek to optimize antimicrobial prescribing in order to improve individual patient care.137 ANTIBIOTIC ALLERGY ALERTS AND DECISION SUPPORT FOR COMPUTERIZED PHYSICIAN ORDERS Antibiotic stewardship programmes may also be complemented by electronic computerized physician prescriptions with decision support systems139 utilizing drug/antibiotic allergy checks.2. A high index of clinical suspicion and immediate withdrawal of the suspected drug/drugs are the most important steps in the management of antibiotic allergy.90:342-7.. Friedmann PS. JAMA 1986. Oakley A. Hughes JM. The diagnosis of DILE is based on a temporal association (months to years) of use of the putative drug with characteristic lupus-like symptoms. Naldi L. Bastuji-Garin S.4168/aair. doi: 10. Braunschweig S.52:388-93.g.438 consecutive inpatients. Among the antibiotics. Melander A. Roujeau JC.140 However. Drug allergy in a general hospital: Results of a novel prospective inpatient reporting system.138 However. Rzany B. Drug-induced cutaneous reactions. De-escalation from broad-spectrum empirical antibiotics to narrow-spectrum. however. A report from the Boston Collaborative Drug Surveillance Program on 15. Such programs are often administered by multidisciplinary teams comprising infectious diseases physicians. and resolution of symptoms upon withdrawal of the drug. Ortega Martell JA. Shear NH. Van Cauwenberge P. Ring J. the data from electronic drug allergy physician reporting systems are often inaccurate or incomplete. There are currently no standard diagnostic criteria for DILE and the pathomechanisms are still unclear. Number 2. reduce hospital costs and slow the spread of antibiotic resistant organisms.org Allergy Asthma Immunol Res. creation of an antimicrobial formulary with restricted prescribing of targeted agents. 1975 to 1982. 6.g.113:832-6. Johansson SG. Molstad S. culture and sensitivity specific antibiotic is a supplemental strategy used in such programmes to reduce antibiotic resistance from the use of broad-spectrum antibiotics. Systemic DILE is characterized by typical lupus-like symptoms including skin signs. Thien F. 8.2.. October 2003.23 Similarly. Rademaker M.357:1851-3. Systemic corticosteroids and immunosuppressive drugs are only needed in refractory cases. 2. de-escalation in a patient with unconfirmed antibiotic allergy should be exercised with caution as drug provocation tests in the presence of negative skin tests.77 . Combination therapy. Duffill MB. 5. Tang CY. Lancet 2001. Kunzi UP. Hunziker T. Strategies for changing antimicrobial prescribing behaviour include education of prescribers regarding proper antimicrobial usage. usually mild systemic involvement and a typical laboratory profile with positive antinuclear and anti-histone antibodies. Systemic immunomodulatory drugs may be required to suppress severe cutaneous/systemic reactions. and infection control practitioners. in particular where no alternative medications are available or are as effective. Chng HH. minocycline and isoniazid are most often associated with DILE. Cutaneous adverse drug reactions in a hospital setting.108:165-6. Lockey RF. N Z Med J 1995. Hoigne R. Thus. Trends in antimicrobial drug prescribing among office-based physicians in the United States. 3. Jick S. JAMA 1995. Comprehensive hospital drug monitoring (CHDM): adverse skin reactions.

Acad Med 2002. Campi P. Kim TB. 2010 April. Pichler WJ. Asthma and Immunology.57:45-51. J Allergy Clin Immunol 2005. 38. Gamboa PM. Demoly P. 15. doi: 10.153:99-105. Negativization rates of IgE radioimmunoassay and basophil activation test in immediate reactions to penicillins. Mayorga C. 11. Blanca M. Int Arch Allergy Appl Immunol 1982. Blanca M. Kim JY. A comparison of the performance of two penicillin reagent kits in the diagnosis of beta-lactam hypersensitivity.17:919-25. Benahmed S. Contact Dermatitis 2001. Greenberger PA. Gilliland AE. Torres MJ. 26. Padial A. 17. and the Joint Council of Allergy. Gomez E. Pichler W. 40. The basophil activation test in immediate-type drug allergy. Zawodniak A.2. Romano A. Bircher A. Cupples ME. Drug hypersensitivity: questionnaire. Fam Pract 2004.54:999-1003. 33. Demoly P. Pharmacoepidemiol Drug Saf 2008. Torres MJ.83:665-700. Bousquet PJ. Fernandez T. Ring J. Position paper: Allergen standardization and skin tests. Pichler WJ. 35.29:517-35.129:92-6. Garcia-Robaina JC. Swierczynska M. Brockow K. ter Riet G. Viola M. In vitro tests in drug hypersensitivity diagnosis. Moreno F. Allergy 2004. Montroni M. Bircher A. 39. Allergy 2007. Brockow K. Immunol Allergy Clin North Am 2009. Pichler WJ. 14. Bousquet PJ. Castells M. Demoly P. Antepara I. 21. Pichler WJ. Demoly P.58:961-72. Perez E. Aberer W.77 http://e-aair. EAACI/GA2LEN guideline: aspirin provocation tests for diagnosis of aspirin hypersensitivity. Fernandez J. Clinical evaluation of Pharmacia CAP System RAST FEIA amoxicilloyl and benzylpenicilloyl in patients with penicillin allergy. Diagnosis of immediate allergic reactions to beta-lactam antibiotics. Sturm G. Canto G. Juarez C.64: 249-53. Allergy 2003.68:352-7.77:742-3. Benzylpenicillin skin testing is still important in diagnosing immediate hypersensitivity reactions to penicillins.29:585-606. Rodriguez JL. 10.48:48-82. The European Academy of Allergology and Clinical Immunology. Asthma and Immunology. Bircher A. Dahlen B. Viola M. Bousquet-Rouanet L. Blanca M. Drug provocation tests in patients with a history suggesting an immediate drug hypersensitivity reaction.34:1768-75. De Weck AL. Picado C.115:1314-6. Guidelines for performing skin tests with drugs in the investigation of cutaneous adverse drug reactions. Allergy 2002. EAACI interest group on drug hypersensitivity. Fernandez J. Allergy 2001. Juarez C. Tilch J.62:1111-8. Kowalski ML. A randomized controlled trial using instant photography to diagnose and manage dermatology referrals. 28. 30. The lymphocyte transformation test in the diagnosis of drug hypersensitivity. Mann T. Torres MJ. Gamboa PM. Bilo MB. 29. Blanca M. 36. De Week AL. Aberer W. Kropf R. Leggett P. Bousquet PJ. Romano A. Demoly P. Importance of mixture of minor determinants and benzylpenicilloyl polyL-lysine skin testing in the diagnosis of beta-lactam allergy. Sanz ML. Demoly P. Romano A. Bridts CH. Cornejo-Garcia JA. Matheu V. J Investig Allergol Clin Immunol 2007. 18. Lochmatter P. Yang KA. Reche M. Ann Allergy Asthma Immunol 1999. Hausmann OV. Fernandez TD. Barbaud A.4168/aair. 32. 27. Blanca M. General considerations for skin test procedures in the diagnosis of drug hypersensitivity. 37. Campi P.2.145:558-64. Allergy 1999. Vega JM. Sanchez-Sabate E. Vega JM. Bae YJ. Allergy 2009. Setkowicz M.29:555-66. Aberer W. Brockow K. and erythema multiforme.58:854-63. de Ramon E. Assessment of a new brand of determinants for skin testing in a large group of patients with suspected beta-lactam allergy. Peek N. Blanca M.45:321-8. Mayorga L. Grammer LC. Stevens-Johnson syndrome. Garcia JJ. 34.7:325-42. Gentinetta T. Wyatt JC. Arnoux B. de Keizer NF. 22. Edwards RG.56:862-70. Eminovic N. Demoly P. Cho YS. Spackman DA. Rodriguez-Bada JL. DeSwarte RD. Drug allergy and protocols for management of drug allergies. Vila L. Corbett R. Pichler WJ. Park CS. Greenberger PA. Allergy 2003. Mayorga C. Blanca M. Co-Minh HB.64:242-8. Bachert C. A comparison between poly-Llysine and human serum albumin as carriers. Valluzzi R. Patterson R. Asthma and Immunology. Skin testing in delayed reactions to drugs. 31. Allergy 2007. Godard P. DeSwarte RD. N Engl Reg Allergy Proc 1986. Romano A. Immunol Allergy Clin North Am 2009. Grammer LC. 25. de la Torre F. Bindels PJ. Teledermatologic consultation and reduction in referrals to dermatologists: a cluster randomized controlled trial. Executive summary of disease management of drug hypersensitivity: a practice parameter. Sahla H. Blanca M. Scadding G. Flow cytometric basophil activation test by detection of CD63 expression in patients with immediate-type reactions to betalactam antibiotics. Kim SL. Steele K. van Weert HC. Clin Exp Allergy 2004. 13. Rapid desensitization for hypersensitivity reactions to medications. Mayorga C. 12. O’Reilly D. 16. Immunol Allergy Clin North Am 2009. Clin Exp Allergy 2002. Blanca-Lopez N. 23. J Immunol Methods 1992. Gaeta F. J Clin Lab Anal 1997. Moon HB. Suau R. Torres MJ. Mayorga C. Drug provocation testing in the diagnosis of drug hypersensitivity reactions: general considerations. Determination of IgE antibodies to the benzyl penicilloyl determinant. Messaad D. Determination of IgE antibodies to the benzylpenicilloyl determinant: a comparison of the sensitivity and specificity of three radio allergo sorbent test methods. Blanca M. Perez E. Poza P. Fernandez J. Goncalo M.140: 1001-6. Caruso C. Management of Antibiotic Allergy Choy AC. the American Academy of Allergy.17:257-60. Bousquet J.2(2):77-86. Bochenek G. Romano A.32:277-86. Sanz ML.AAIR Clinical classification of cases of toxic epidermal necrolysis. The diagnostic interpretation of basophil activation test in immediate allergic reactions to betalactams. Daures JP.15:239-64. Patterson R. 24. the American Academy of Allergy.2010. Sanchez-Machin I. A picture is worth more than a thousand words: enhancement of a pre-exam telephone consultation in dermatology with digital images. Weck A. Garcia-Aviles C. Allergy Proc 1994. Allergy 2009. Allergy Asthma Immunol Res. Joint Task Force on Practice Parameters.org 83 .29:53754. Brockow K. Wohrl S. McGlade K. Romano A. Bruijnzeel-Koomen CA. Romano A.11:251-7. Brown JE. Allergy 1993. Demoly P.59:809-20. Ann Intern Med 2004. Uasuf C. Bruynzeel D. Barbaud A. Szczeklik A. Drug allergy and protocols for management of drug allergies. Moya MC. 9. Torres MJ. Chazot M. Nizankowska-Mogilnicka E.21:54-6. Gaeta F. Development and use of three new radioallergosorbent tests in the diagnosis of penicillin allergy.62:53-8. Carmona MJ. 19. Juarez C. Ebo DG. The use of an electronic medical record system for mandatory reporting of drug hypersensitivity reactions has been shown to improve the management of patients in the university hospital in Korea. Garcia J. Perez-Estrada M. Gonzalez R. Mayorga C. Arch Dermatol 2009. Stevenson M. Mastalerz L. Ring J. Manfredi M. Antunez C. Arch Dermatol 1993. Immunol Allergy Clin North Am 2009. Colven R. Dewdney JM. 20.

Romano A. Paquet P. Leynadier F. Abuaf N. Comparison of two basophil activation markers CD63 and CD203c in the diagnosis of amoxicillin allergy. Blanca M. Gonzalez I. de la Fuente J. Allergy 2009. Pediatrics 2009. 73. Campi P.10: 531-40.17:393-8. Mirakian R.19:91-109. Madalon M.2010. Thomson W. 77. 69. Li WK. Naldi L. Sainte-Laudy J. Br J Dermatol 2002. Romano A. Kelly JP.38:921-8. Korman TM. 74. Gueant JL. The EuroSCAR-study.15:146-9. Rajoely B. Halevy S. Pichler WJ. Patriarca G. Hypersensitivity reactions to quinolones. Wortham DW. 58. 46. Gonzalez Mahave I. Allergy 2004.97:23-7. Volume 2. J Allergy Clin Immunol 1995. Pirmohamed M. Leyden JJ. Dash CH. Rieder MJ. Gaeta F. 62. Perez-Inestrosa E. Cephalosporin chemical reactivity and its immunological implications. Pichler WJ. Weber EA. Lin D. Shapiro LE. Adelman DC. Jawaid A. Cutaneous adverse reactions to clindamycin: results of skin tests and oral exposure. Safety of doxycycline and minocycline: a systematic review. doi: 10.354:2835-7. TNF. StevensJohnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. del Pozo Gil MD.133:122430. Martin-Esteban M.95:668-71. MartinezVazquez C. Quiralte J. Toxic epidermal necrolysis following clindamycin treatment. J Investig Allergol Clin Immunol 2007. 71. Dendle C. Saxon A. Alsbou M. Beall GN. Contact Dermatitis 2005. Hodgkinson M. J Allergy Clin Immunol 2006. 51. Stalford A. Delrieu O.128:35-44.123:e297-304. Cotrimoxazole for prophylaxis or treatment of opportunistic infections of HIV/AIDS in patients with previous history of hypersensitivity to cotrimoxazole. Medications as risk factors of Stevens-Johnson syndrome and toxic epidermal necrolysis in children: a pooled analysis. WMJ 1998. Park BK. Sim E. 50.4168/aair. Alfirevic A. Demoly P. Youlten LJ. Nestorovic B. Diagnosis of nonimmediate reactions to betalactam antibiotics. Saxon A. 63. Torres MJ. Ewan PW. 42. Flahault A. Clin Exp Allergy 2006. Gueant JL. Comparative safety of tetracycline. cell-mediated hypersensitivity to beta-lactams. Depta JP. Shear NH. Araujo L. 44. Br J Dermatol 1995. MacArthur RD. Crespo JF.82:213-7. Blasco Sarramian A. Kalimo K. Clin Exp Allergy 2008. Svensson CK.2. Blanca M. Viola M. Trautmann A.66:323-4. 84 http://e-aair. 48. Brocker EB. Mockenhaupt M. critical review of the literature. Pharmacogenetics 2000. J Clin Pharmacol 2002. Montanez MI. Immediate hypersensitivity reactions to beta-lactam antibiotics. Crane LR. Ann Intern Med 1987. Report of oral clarithromycin desensitization. Gaouar H. LTA. Lammintausta K. Roujeau JC. Ryan C. Gaeta F. Greenberger PA. Mazur N. Pettinato R. Curr Pharm Des 2006. Regalado J. Roujeau JC. Lobera Labairu T.10:705-13. Dermatol Online J 2008. Diagnosis of immediate-type beta-lactam allergy in vitro by flow-cytometric basophil activation test and sulfidoleukotriene production: a multicenter study. treatment. 75. Pierard GE. 65. Seitz CS. Friedmann PS. 2010 April. Adelman DC. O’Neil WM. Schiavino D. Rohr AS.org Allergy Asthma Immunol Res. J Invest Dermatol 2008. Phillips EJ. Blasco A. Macrolides allergy. Girot R. Clin Exp Allergy 2009. Pirmohamed M. English JS. Merk H. Martin E. Knowles SR. Buonomo A.146:643-8. Tolerability of meropenem in children with IgE-mediated hypersensitivity to penicillins. Lombardo C. 54. Imipenem cross-reactivity with penicillin in humans. Clindamycin desensitization in an AIDS patient. Dugue P. Pascolini L. Lobera T.53:335-8. Arch Dermatol 1997. Gaeta F. Shear NH.42:613-9. Valluzzi R. 60. Alfirevic A. Gonzalez R. Doll MA. Kelkar PS. Sulfa hypersensitivity in patients with HIV infection: onset.132:665-6. Mayorga C. Schaaf-Lafontaine N. Montanez MI. 47. 53. Holmes NE. Kerdel FA.2. Hein DW. J Investig Allergol Clin Immunol 2009. Weber JM. Viola M. Schmid DA. Clindamycin skin testing has limited diagnostic potential. Bouwes Bavinck JN.27:1329-42. 72. Wilkins EG. minocycline.1:107-18. Demoly P. Sopena B. AIDS 41. Patel A. J Allergy Clin Immunol 1988.14: 2840-62. Torres MJ. Vilar J. 45. 52. Pascual C. Bircher A. Clindamycin hypersensitivity appears to be rare. Wheeler G. Blanca-Lopez N. Calandra GB. Dunant A. Ollier WE.77 . Sulewski RJ Jr. Acute generalized exanthematous pustulosis due to clindamycin. Blyumin M. Venturini Diaz M. 61.117: 404-10. 67. Ann Allergy Asthma Immunol 1999. Rostane H. Li JT. Farrough MJ.59:1153-60. Trautmann A. April 2010 57.Thong Drouet M. Nasser SM. Pharmacogenomics 2009. Pichler WJ. Tokola R. Clin Ther 2005. Brocker EB. 56. Park BK. Allergy diagnostic testing in clindamycin-induced skin reactions.39:43-61. Clin Exp Allergy 2009. N Engl J Med 2006. T cell-mediated hypersensitivity to quinolones: mechanisms and cross-reactivity. Altomonte G.107: 204-15. Lopez C.345:804-9. Br J Clin Pharmacol 2008. Romano A. J Antimicrob Chemother 1975. Cross-reactivity and tolerability of imipenem in patients with delayed-type. Luna I. Allergy 2008. Blanca M. Penicillin allergy and the cephalosporins. Gueant-Rodriguez RM. Durham SR. Knowles SR.82:443-5. del Pozo MD. Vilar FJ. Notman MJ. Curr Pharm Des 2008. Gueant-Rodriguez RM.63:237-40. Rodriguez R. 149:246-50. Bastuji-Garin S. Autegarden JE. Antunez C. Medjo B. Acetylator phenotype and genotype in HIV-infected patients with and without sulfonamide hypersensitivity. Marcos C. Viola M.36:59-69. N Engl J Med 2001. 55. In vitro detection of specific IgE antibodies to erythromycin.2(2):77-86. Immediate allergic reactions to cephalosporins: evaluation of cross-reactivity with a panel of penicillins and cephalosporins. Romano A.146:266-9. 43.39:1738-45. Brockow K. Torres MJ. Brief communication: tolerability of meropenem in patients with IgE-mediated hypersensitivity to penicillins. Nucera E. Flahault A. 64. Number 2. Int Arch Allergy Immunol 2009. 66. Ann Intern Med 2007. 49. Association analysis of drug metabolizing enzyme gene polymorphisms in HIV-positive patients with co-trimoxazole hypersensitivity. Cochrane Database Syst Rev 2007:CD005646.12:3313-26. BSACI guidelines for the management of drug allergy. Fretland AJ. 70. Fernandez T. Aberer W. and doxycycline. Maison P. Atanaskovic-Markovic M. 76. Suau R. Huber PA. In vivo diagnostic tests in adverse reactions to quinolones. Imipenem in patients with immediate hypersensitivity to penicillins. Hajdu R. Kaufman DW. Viboud C. Cephalosporin allergy. Sidoroff A. Diagnostic testing in suspected fluoroquinolone hypersensitivity. Mockenhaupt M.5: 323-30. Decinti M. Schneck J. Jermann TM. HSPA1L and HLA-DR gene polymorphisms in HIV-positive patients with hypersensitivity to cotrimoxazole. Curr Opin Allergy Clin Immunol 2005. J Investig Allergol Clin Immunol 2005. Bowman CE. 59.64:1644-8. Seitz CS.14:14. Levi N. Immediate hypersensitivity to quinolones: moxifloxacin cross-reactivity. Mayorga C. 68. Romano A. Graziano FM. Schmid DA. Perez-Inestrosa E. Smith K.

97. Perrett CM.18:71-2. Chopra N. 98. Kuaban C.145:1030-6. Marshall C. Kimura S. Stevens-Johnson syndrome and toxic epidermal necrolysis in Thailand. Shiohara T. Oppenheimer J.29:633-6. Immediate hypersensitivity to rifampicin in 3 patients: diagnostic procedures and induction of clinical tolerance. Malasky C.97:681-7.328:1292. Neu HC. Glycopeptide-induced vasculitis cross-reactivity between vancomycin and teicoplanin. Greenberger PA. J Antimicrob Chemother 1991. Vossen JM. Ota Y. Chang YS. J Antimicrob Chemother 1991. Lee SM. Ruiz A. 93. Goldberg D. 113. Chung WH. Hong SJ. Song WJ. Oral desensitization to rifampin and ethambutol in mycobacterial disease.28:476-7. McGrath KG. Bielory L. Patterson R.4:67-71. Kita H.74:474-7. Expert Opin Drug Saf 2006. BMJ 2004. 81. Schreiber J. IgE-mediated reaction to vancomycin and teicoplanin after treatment with vancomycin. Scherer K.AAIR 1995. Kekkaku 2004. Kim HB. Kada N. Shigeto E.7:317-23. Teicoplanin induced drug hypersensitivity syndrome. Danielson DR.53:4069-79. Shiohara T. Chida K.98:1518-9. Reisman RE.140:20-6. Pediatr Infect Dis J 1994.5:231-49. Chest 1990. Kim YY. Laffond E.9:1201-2. 108. Magnussen R.21:110810.58:540-1. Anne S. 2010 April. Nakamura H. Bircher AJ. 91. Med Clin (Barc) 1992. Miwa S. Min KU. Daghigh B. Orfan NA. Markus P. Chu CY. Fillet G. Jean SS. Photodermatol Photoimmunol Photomed 1998. Sun CC. rifampin. Schroeder DR. Paul M. Greenberger PA. 104. Rosenwasser LJ.77 http://e-aair. Suda T. Detjen PF. Allergic cross-reactivity of teicoplanin and vancomycin. Hayakawa H. A case of hypersensitivity syndrome to both vancomycin and teicoplanin. Int J Dermatol 1993. Allergol Int 2006.79:7-10. Chest 2008. Adverse reactions to first-line antituberculosis drugs. Schlaak M. Martin JA. Holland CL. [The usefulness of lymphocyte stimulation test (LST) in side effects of antituberculosis drugs].2010. Matsushima T. Ikizoglu G. Park MA. McBride SR. Hausermann P. Borish LC. Kano Y. Lorente F. Demirkan F. Chen YT. 96. Middleton E Jr. 116. Davila I. Ganz MA. Allergic cross-reaction of teicoplanin and vancomycin. Fujita K. Cytomegalovirus disease during severe drug eruptions: report of 2 cases and retrospective study of 18 patients with drug-induced hypersensitivity syndrome. 88. Descriptive and therapeutic controversy. Anaphylactoid reactions to glycopeptide antibiotics. Leenutaphong V. Eur J Med Res 1999. Park M.83:651-62. Autoimmun Rev 2009.75:699-704. Pelton S. Nishimura K. Stevens-Johnson syndrome (SJS): effectiveness of corticosteroids in Allergy Asthma Immunol Res. Kwon HS. Kawahara S. 92. Am J Respir Crit Care Med 1994. Frigas E. Kaya TI. Shishido S. Teicoplanin-induced anaphylaxis. Plunkett RW. 85. J Korean Med Sci 2006. Batista JC. 100. Collignon J. Kano Y. Stoloff RS. Rapid oral desensitization to isoniazid. Suzuki Y. Bercion R. 99.24:395-6. Vancomycin anaphylaxis and successful desensitization in a patient with end stage renal disease on hemodialysis by maintaining steady antibiotic levels. Morisawa Y. 105. Allergy 2003. Dermatology 2001. Am J Med Sci 2002. 107. Two patients with isoniazid-induced photosensitive lichenoid eruptions confirmed by photopatch test. Intern Med 2006.27 Suppl B:17-29.202:141-2. 37:82-3. Miller TP.149:815-7. 79. [Clindamycin desensitization in a patient with the acquired immunodeficiency syndrome]. 110. Viral connection between drug rashes and autoimmune diseases: how autoimmune responses are generated after resolution of drug rashes. Reaction to teicoplanin with tolerance to vancomycin. Okimoto N.55:1-8.14:77-8. Teicoplanin-induced skin eruption. J Investig Allergol Clin Immunol 2008. Ann Allergy Asthma Immunol 2000. 84. Chest 1990. Takeyama H. Comparative efficacy and safety of vancomycin versus teicoplanin: systematic review and meta-analysis. Callen JP. Kobayashi K. Buergin S.32:428-31. Polk RE. Wu J. Successful vancomycin desensitization with a combination of rapid and slow infusion methods. Int Arch Allergy Immunol 2006. Pedersen M. Kim JH. Black DR.org 85 . Forget EJ. Antimicrob Agents Chemother 2009. Li JT. Routes JM. 102. Lancet 1986. Kobashi Y. 89.323:273-8. Menzies D. East Afr Med J 1997. Grek V. Vancomycin anaphylaxis and successful desensitization. Moreno E. Fine PL.134:1027-32. Sunthonpalin P. 114. Kato K. Galbraith K. van Weel-Sipman MH. Preoperative evaluation of patients Management of Antibiotic Allergy with history of allergy to penicillin: comparison of 2 models of practice. Shishido S. Koulla-Shiro S. Yano S. Street A. Rapid oral desensitization to isoniazid and rifampin. Ann Allergy 1994. Vancomycin-induced linear IgA bullous disease presenting as toxic epidermal necrolysis. 111. Erythema multiforme and Stevens-Johnson syndrome.2. Shiohara T. Grammer LC. Matesic D. 106. Sonenthal KR. Koike K. 83. Drug lymphocyte stimulation test in the diagnosis of adverse reactions to antituberculosis drugs. Curr Opin Allergy Clin Immunol 2007. Markus PJ. Safety and effectiveness of a preoperative allergy clinic in decreasing vancomycin use in patients with a history of penicillin allergy. Leibovici L. Gonzalzles A. 78.98:331-6. doi: 10. 109. Alonso MD. Shirai M. Antela A. Kim HB. Inaoka M. Bullous skin disease: an unusual allergic reaction to vancomycin. 117. Muller-Quernheim J. Mayo Clin Proc 2008. Clin Exp Dermatol 2004. Waldman MA. Zissel G. Ann Allergy Asthma Immunol 2006. 115. 90. Kagawa H. Lee AY. Yoshida A. 80. 112. Int J Dermatol 2002. Jeong YY. Murakami M. Beutner EH. Olson KE.4168/aair.13:167.1:47.8:488-94. Greinert U. 86. Narr BJ. Negron G. de Vries E. Unal S. and ethambutol.45:317-21. Scand J Infect Dis 1992.84:633-5. Ogunkoya A. Ann Pharmacother 2001.35:1458-64. Volcheck GW. Tatsukawa T. Macias E. J Infect 1998.41:948-9. Arch Dermatol 2009. Desensitization protocols for vancomycin hypersensitivity.2(2):77-86. Kitazawa T. Cameroon. Neughebauer BI. Andrien F. Suthipinittharm P. 87. Allergy 2006.98:478-9. Zeiss CR. McElrath MJ. Grammer LC.73:402-4. Hung SI. Knudsen JD. Navas E. Kim BS. 94. Aota N.2. A four-year-old child with teicoplanin allergy but no evidence of cross-reaction with vancomycin. Drug-induced hypersensitivity syndrome (DIHS): a reaction induced by a complex interplay among herpesviruses and antiviral and antidrug immune responses. Jung SY. Human leukocyte antigens and drug hypersensitivity.61:1370. Wazny LD. Kuraoka T. Acute generalized exanthematous pustulosis due to teicoplanin. Kekkaku 2000. [Desensitization therapy for allergic reactions of antituberculous drugs--evaluation of desensitization therapy according to the guideline of the Japanese Society for Tuberculosis]. Svetitsky S. 103. Ohba H. Sivayathorn A. Derimanov GS. Matz J. Asero R. Dykewicz MS. Walker CL. 95. Cho SH. Kim YK. 82. Asano Y. Green D. 101. Patterson R. HIV seroprevalence rate and incidence of adverse skin reactions in adults with pulmonary tuberculosis receiving thiacetazone free anti-tuberculosis treatment in Yaounde. Abe T. Lawrence ID. Lymphocyte transformation test for the evaluation of adverse effects of antituberculous drugs.

Schuhmacher MH. 138. Sheha H. 122. Amniotic membrane transplantation as a new therapy for the acute ocular manifestations of Stevens-Johnson syndrome and toxic epidermal necrolysis. Greenberger PA. Heng WJ. Plasma exchange in patients with toxic epidermal necrolysis. Proc AMIA Symp 2000:2-6. Karagianni A. 131. Br J Dermatol 1998. 126. Toxic epidermal necrolysis and cyclosporin. doi: 10. Ficheur G. Giorio G. Treatment of toxic epidermal necrolysis with intravenous immunoglobulin in children.2010. 125. McGrath KG.148:102-11. 119. Kuperman GJ.21:101-5. Hunziker T. Kaplan M.45:25-48. Martin MT. Romanelli P. Sombolos K. Teich JM. Christidou F. Latarjet J. 128.48:1122-8. Yip LW. Daoud YJ.54:686-96. Patterson R. Sullivan JR. Stud Health Technol Inform 2009. 124. Kerdel FA. Trent JT. The outcome of Stevens-Johnson syndrome treated with corticosteroids. Natse T. Milpied B.4168/aair. Serrot E. Duguet C.37:208-12. 140. Hynes AY. Boudeau S. Arch Dermatol 2003.203:45-9. Stella M. Lamotrigine-induced toxic epidermal necrolysis treated with intravenous cyclosporin: a discussion of pathogenesis and immunosuppressive management. Snow J. Bates DW.139:1127-8. Chng HH. Br J Dermatol 2005. 139. Kerdel FA. Allergy Proc 1992. 133. Morris SE. Improving allergy alerting in a computerized physician order entry system. Arch Dermatol Res 2009. Drew RH. Australas J Dermatol 1996. Grammer LC. 132. Kirsner RS. Surv Ophthalmol 2009. Reed R. Tan AW. Arch Dermatol 2003. Lancet 1998.47:548-52. Saurat JH. Bamichas G. Koukourikos S. Tripathi A. Xu J. Latall J. Grammer LC. Randomised comparison of thalidomide versus placebo in toxic epidermal necrolysis. Brun-Buisson C. Chazard E. Allergy Proc 1995.153:241-53. Flynn K. Arch Dermatol 2003. 118. Intravenous immunoglobulin treatment for Stevens-Johnson syndrome and toxic epidermal necrolysis: a prospective noncomparative study showing no benefit on mortality or progression.2. 129. 135. Schena D. Corticosteroid therapy in an additional 13 cases of Stevens-Johnson syndrome: a total series of 67 cases. Hutchinson PE.77 . Grammer LC.2. Sandige H. Bollero D. Chaidemenos G. Patterson R. 121.org Allergy Asthma Immunol Res. Effectiveness of early therapy with corticosteroids in Stevens-Johnson syndrome: experience with 41 cases and a hypothesis regarding pathogenesis. Revuz J. Beuscart R. April 2010 mal necrolysis treated with intravenous high-dose immunoglobulins: our experience. et al. 127. Zaki I. Dermatology 2001. Wolkenstein P.6:225-8. Dalziel KL. Clemente A. Foster CS. Roujeau JC.2(2):77-86. Abookire SA. Ther Apher 2002. Saffle JR. Merlin B. practical management and future directions. Ann Allergy 1994. Gregory DG.13:89-95. Severe bullous drug reactions treated successfully with cyclophosphamide. Trent J. Tristani-Firouzi P. Chrysomallis F. Ha T. Del Giglio M. Controversy in the use of high-dose systemic steroids in the acute care of patients with StevensJohnson syndrome. Maignan M. Treatment of toxic epidermal necrolysis with high-dose intravenous immunoglobulins: multicenter retrospective analysis of 48 consecutive cases. Margolis DJ. Watson A. Mauri DN.139:33-6.301:99-105. 137. 2010 April. Paterno MD. Trautmann A. Analysis of intravenous immunoglobulin for the treatment of toxic epidermal necrolysis using SCORTEN: The University of Miami Experience. Adverse drug events prevention rules: multi-site evaluation of rules from various sources. Cheriyan S. Petersen MJ. Doan T. Padilla RS. Hall AP. Eye (Lond) 2005. Int Ophthalmol Clin 2005. Int J Dermatol 2009. Toxic epider- Volume 2. Liang L.Thong management and recurrent SJS. Vaillant L.352:1586-9. Zone JJ.139:39-43. Toxic epidermal necrolysis: current evidence. J Am Acad Dermatol 2002. Girolomoni G. Cassano P. 123. Thong BY. Toxic epidermal necrolysis associated with severe hypocalcaemia. Number 2. Greenberger PA. Kafkala C. J Manag Care Pharm 2009. Latall J. Pilorget A. Li F. Zeiss CR.139:26-32. French LE. Kheirkhah A.19:846-53.133:337-8. 120.22:254. Patel S. Viard I. Jarrett P. Ditto AM. Miller M. Hogan MB. Br J Dermatol 1995. Stangou M. Allergy Asthma Proc 2000.15:S18-23. Kampgen E. Revuz J. Antimicrobial stewardship programs: how to start and steer a successful program. Zhu X.73:27-34. High-dose intravenous immunoglobulin in the treatment of toxic epidermal necrolysis: a study of ocular benefits. 136. 134. Greenberger PA. Clin Exp Dermatol 1997. Roujeau JC. 86 http://e-aair. Chave TA. Sladden MJ. Chimenti S. Vedove CD. Klein CE. Khin LW. Detjen P. Combination therapy of intravenous immunoglobulin and corticosteroid in the treatment of toxic epidermal necrolysis and Stevens-Johnson syndrome: a retrospective comparative study in China. Brown J.16:151-5. Bocquet H. Shay E. and treated with cyclosporin. Mortimer NJ. Yang Y. Prins C. 130. Bachot N. Patterson R. Drug-induced lupus erythematosus. Brocker EB. Tseng SC.