In this case report, we report a delayed maculopapular skin eruptions caused by clindamycin in a 12-year-old girl. J Allergy Clin Immunol Pract. Contact Derm. Abarro and Seoane describe a case of a patient who experienced immediate urticaria following topical nasal application of neomycin and who had positive skin prick test (SPT) to neomycin sulfate [23]. There have been increasing numbers of case reports of AGEP with clindamycin in the recent literature [4753]. This review covers the most commonly reported hypersensitivity reaction types including epidemiological data and published evaluation/diagnostic strategies and desensitization protocols for each of these antimicrobial groups. report a case of perioperative clindamycin anaphylaxis with localized hives along the infusion site, hypotension, hypoxia, and vomiting within 5min after antibiotic administration [40]. Infection. Pharmacotherapy. Corazza et al. As there are no equally effective alternatives that have been systematically evaluated for the treatment of Trichomonas vaginalis, the CDC states that patients with an IgE-mediated reaction to a nitroimidazole may need to undergo metronidazole desensitization using published protocols [88]. Skinmed. Monteagudo B, Cabanillas M, Iriarte P et al (2018) Clindamycin-induced maculopapular exanthema with preferential involvement of striae distensae: a koebner phenomenon? When combined with other agents, aminoglycosides can have effects against gram-positive organisms such as Staphylococcus aureus, Streptococci, and Enterococci [2]. J Allergy Clin Immunol. Drugs causing fixed eruptions: a study of 450 cases. A potential for cross-reactivity exists between metronidazole and other imidazoles, such astinidazole, clotrimazole, ketoconazole,miconazole, andalbendazole [8, 87] given structural similarities [8]. Esty B, Minnicozzi S, Chu EC, Broyles AD, Yee CSK. Cutaneous adverse reactions to antibiotics Morbilliform eruption Acute urticaria Fixed drug eruption Who gets adverse drug reactions? describe a case of a patient previously sensitized to topical neomycin with widespread eczematous dermatitis from gentamicin cream with confirmed positive patch testing to gentamicin [13]. Immediate and delayed skin allergic reactions to Clindamycin have been rarely reported in pediatrics. Probable metronidazole induced serum sickness-like reaction in a paediatric patient. J Investig Allergol Clin Immunol. Thorax. Immediate-type skin testing is used to evaluate immediate reactions. There is also no validated serum IgE testing for these antibiotics. 2023 Springer Nature Switzerland AG. Prieto A, De Barrio M, Infante S, Torres A, Rubio M, Olalde S. Recurrent fixed drug eruption due to metronidazole elicited by patch test with tinidazole. Other case reports include allergic contact dermatitis [75], fixed drug eruption [7679], serum sickness-like reaction [80], SJS/TEN [81, 82], AGEP [83, 84], SDRIFE [85], and a possible case of DRESS given fever and rash but no lab studies were done to assess internal organ involvement [86]. Considerations for antibiotic alternatives [92], Pseudomonas aeruginosa: cefepime, ceftazidime, ciprofloxacin, piperacillin/tazobactam, meropenem/imipenem, Acinetobacter: TMP/SMX, ceftriaxone/cefotaxime (in addition to above), Enterobacter, Citrobacter, or Serratia: cefuroxime (in addition to above), Klebsiella: cefazolin/cephalexin (in addition to above), Escherichia coli or Haemophilus influenzae: ampicillin, amoxicillin/clavulanate (in addition to above), MRSA or CoNS: vancomycin, linezolid, daptomycin, ceftaroline, MSSA: cefazolin/cephalexin, oxacillin (in addition to above), Streptococcus pneumoniae or pyogenes: penicillin, ampicillin, amoxicillin/clavulanate (in addition to above), Anaerobic streptococci: penicillin, ampicillin, amoxicillin/clavulanate, cefazolin, cefoxitin, ceftriaxone/cefotaxime, meropenem/imipenem, piperacillin/tazobactam, metronidazole, vancomycin, Bacteroides fragilis: penicillin, ampicillin, amoxicillin/clavulanate, cefoxitin, meropenem/imipenem, piperacillin/tazobactam, metronidazole, Clostridia tetani or perfringens: penicillin, ampicillin, amoxicillin/clavulanate, cefoxitin, ceftriaxone/cefotaxime, meropenem/imipenem, piperacillin/tazobactam, metronidazole, vancomycin, MRSA or CoNS: vancomycin, clindamycin, daptomycin, ceftaroline, Enterococcus faecalis or faecium: penicillin, ampicillin, amoxicillin/clavulanate, vancomycin, daptomycin, Clostridium difficile: vancomycin, meropenem/imipenem, Clostridia tetani or perfringens: penicillin, ampicillin, amoxicillin/clavulanate, cefoxitin, ceftriaxone/cefotaxime, meropenem/imipenem, piperacillin/tazobactam, clindamycin, vancomycin, Bacteroides fragilis: penicillin, ampicillin, amoxicillin/clavulanate, cefoxitin, meropenem/imipenem, piperacillin/tazobactam, clindamycin, Anaerobic streptococci: penicillin, ampicillin, amoxicillin/clavulanate, cefazolin, cefoxitin, ceftriaxone/cefotaxime, meropenem/imipenem, piperacillin/tazobactam, clindamycin, vancomycin, MRSA methicillin-resistant staphylococcus aureus, CoNS coagulase-negative staphylococcus aureus, General considerations for alternative antibiotics with similar coverage; however, alternatives largely depend on specific infection, susceptibilities, and possible toxicities. Ann Pharmacother. Washington NR, Petersen K, Petersen M. The clindamycin catastrophe: a case of antibiotic-induced skin eruption. Ten minutes after each infusion was completed, the subsequent dose was given, for a total of 8h. An inhaled tobramycin desensitization protocol has also been performed successfully in a pediatric patient with cystic fibrosis pulmonary exacerbation [17] (Table (Table33). https://doi.org/10.1053/j.ajkd.2009.07.013, Bagwell AD, Stollings JL, White KD et al (2013) Linezolid desensitization for a patient with multiple medication hypersensitivity reactions. There are case reports of patients who experienced immediate clinical hypersensitivity reactions to gentamicin, tobramycin, neomycin, and streptomycin in which IgE-mediated allergy was confirmed by positive SPT [1921, 23]. J Investig Allergol Clin Immunol. Pseudomembranous colitis and neuropathy have also been reported. describe a patient with hypotension, confusion, dyspnea, and copious oral secretions 3min after a dose of IV Clindamycin for a periodontal abscess [39]. Christiansen el at describes a patient previously exposed to gentamicin in bone cement with hypotension, generalized erythema, and angioedema a few minutes after IV gentamicin also used for surgical prophylaxis [20]. Many of the reports of localized and systemic reactions to aminoglycosides occurred in patients with known prior exposure to some dosage form of an aminoglycoside, usually a topical dosage form, likely causing sensitization [7]. Am J Med. BMJ Case Rep. https://doi.org/10.1136/bcr-2019-230077, Aiempanakit K, Apinantriyo B (2020) Clindamycin-induced acute generalized exanthematous pustulosis: a case report. https://doi.org/10.2340/00015555-1363, Miller Quidley A, Bookstaver BP, Gainey AB, Gainey MD (2012) Fatal clindamycin-induced drug rash with eosinophilia and systemic symptoms (DRESS) syndrome. Romita P, Ettorre G, Corazza M, Borghi A, Foti C. Allergic contact dermatitis caused by clindamycin mimicking retinoid flare. Other immunologic drug reactions that have been reported include fixed drug eruptions [42]. If SPTs are negative, intradermal tests (IDTs) can be performed with nonirritating concentrations. Metronidazole is bactericidal. https://doi.org/10.1016/s0091-6749(03)01783-4 (PMID: 13679828), Solensky R (2020) Hypersensitivity reactions to macrolides, aminoglycosides, tetracyclines, clindamycin, and metronidazole. https://doi.org/10.1007/s15010-015-0826-2, Ebo DG, Mertens C, Braes M, Mennes I, Bridts CH, Sabato V (2019) Clindamycin anaphylaxis confirmed by in vivo and in vitro testing. https://doi.org/10.1086/345744, Bishop E, Melvani S, Howden BP, Charles PGP, Grayson LM (2006) Good clinical outcomes but high rates of adverse reactions during linezolid therapy for serious infections: a proposed protocol for monitoring therapy in complex patients. https://doi.org/10.1345/aph.1S033, Guvenir H, Dibek Misirlioglu E, Toyran M, Kocabas CN (2016) Linezolid desensitization in a pediatric patient. The protocol by Bagwell et al. Retrieved from https://pubchem.ncbi.nlm.nih.gov/compound/Neomycin, Childs-Kean LM, Shaeer KM, Varghese Gupta S, Cho JC (2019) Aminoglycoside allergic reactions. A case of DRESS weeks after starting amikacin was described and consisted of a maculopapular rash, facial edema, fever, hypereosinophilia, transaminitis, and coagulopathy [24]. https://doi.org/10.1177/0009922818805204, Monteagudo B, Cabanillas M, Iriarte P et al (2018) Clindamycin-induced maculopapular exanthema with preferential involvement of striae distensae: a koebner phenomenon? Thorough clinical examination, blood tests and prick, intradermal and patch tests were performed in 3 patients. J Vicente 1 , J L Fontela Affiliation 1Allergy Section, Hospital Virgen de la Luz, Cuenca, Spain. devised an IV metronidazole desensitization protocol described in Table Table88 [91]. Dermatol Online J. PMID: 18718198, Alniemi DT, Wetter DA, Bridges AG et al (2017) Acute generalized exanthematous pustulosis: clinical characteristics, etiologic associations, treatments, and outcomes in a series of 28 patients at Mayo Clinic, 19962013. Acute febrile neutrophilic dermatosis or Sweet syndrome characterized by fever, leukocytosis with neutrophilia, and tender erythematous skin lesions with histologically dense dermal neutrophilic infiltration. Clindamycin is a derivative of lincomycin with a 7(S)-chloro-substitution of the 7(R)-hydroxyl group [31] (Fig. https://doi.org/10.1136/thx.2004.027953, Solensky R, Khan DA (2010) Drug allergy: an updated practice parameter. Tobramycin and amikacin are available in inhaled forms, such as nebulized solutions and inhalation powders or suspensions to treat pulmonary infections [7]. If SPTs are negative, intradermal tests (IDTs) can be performed with nonirritating concentrations. and positive intradermal reactions after 24 h to clindamycin were observed in the second and . The patient was successfully desensitized using an escalating, 14-dose procedure [71]. Contact Derm. There are a few cases of linezolid desensitization described in the literature. Linezolid desensitization for a patient with multiple medication hypersensitivity reactions. Eur Ann Allergy Clin Immunol. In a case series of metronidazole desensitization among 15 patients, 8 use the oral protocol by Kurohara et al. Available on PubMed at: Kostaki M, Polydorou D, Adamou E, Chasapi V, Antoniou C, Stratigos A. Serotonin syndrome can occur, and concurrent use is contraindicated with many anti-depressants [63]. https://doi.org/10.1002/pds.1117, Article J Allergy Clin Immunol. Two of the 31 patients had delayed reactions of erythema, edema, and pruritus that occurred after 72 from the clindamycin intradermal skin testing [58]. Patch testing can be useful to evaluate delayed cutaneous reactions, and patch testing concentrations have been reported for aminoglycosides, clindamycin, and metronidazole. Structural groups: a streptidine; b, c, and d deoxystreptamines. For aminoglycosides, allergic contact dermatitis is the most frequent reaction for which patch testing can be a useful step in evaluation. However, the skin testing for the drugs discussed in this review are not standardized or validated and the positive and negative predictive values are largely unknown. Among 13 patients with delayed reactions, none of the patients had a positive SPT although 3 of the patients had a positive oral challenge [58]. Neomycin-induced contact dermatitis occurs especially in patients with atopic eczema, chronic conjunctivitis or otitis, leg ulcers, and long-term cutaneous use of the drug [1]. A potential for cross-reactivity exists between metronidazole and other imidazoles, such astinidazole, clotrimazole, ketoconazole,miconazole, andalbendazole [8, 87] given structural similarities [8]. J Clin Pharm Ther. Although allergic reactions caused by clindamycin are rare, immediate and delayed skin reactions has been previously reported [2-9]. Allergic contact dermatitis, a type IV hypersensitivity reaction, is the most frequent reaction associated with this class of antimicrobials [8]. For linezolid, cases of hypersensitivity were exceedingly rare and included urticaria, angioedema, anaphylaxis, delayed rashes, and DRESS. J Clin Pharm Ther. Pharm: J Pharm Educ Practice. Clindamycin is frequently implicated in antibiotic-associated diarrhea due to Clostridium difficilecolitis which can cause pseudomembranous colitis. Download available Content available from Clinical Reviews in Allergy & Immunology This content is subject to copyright. 72 Apart from exanthematous eruptions, cases reported in the literature include contact dermatitis, . Therefore, all deoxystreptamine-containing aminoglycosides are contraindicated if a patient has a known hypersensitivity to another deoxystreptamine-containing aminoglycoside [1, 7]. Clin Pediatr. Infectious disease recommendations are useful for individual cases. Protocols for IV tobramycin desensitization have been reported. Oral challenge in a controlled and monitored environment may be useful for provoking and diagnosing hypersensitivity reactions to these antibiotics. Guvenir et al. Structural groups: a streptidine; b, c, and d deoxystreptamines. Tel +972-54-5968961. Notman MJ, Phillips EJ, Knowles SR, Weber EA, Shear NH. Metronidazole diffuses across cell membranes and is partially reduced by anaerobic bacteria and protozoa generating toxic free radicals and disrupting nucleic acid synthesis [72]. Management of trichomonas vaginalis in women with suspected metronidazole hypersensitivity. Historically, AGEP has rarely been associated with clindamycin. There have been increasing numbers of case reports of AGEP with clindamycin in the recent literature [47,48,49,50,51,52,53]. Br Med J. https://doi.org/10.1136/bmj.2.5711.703, Mazur N, Greenberger PA, Regalado J (1999) Clindamycin hypersensitivity appears to be rare. De Cruz R, Ferguson J, Wee JS, Akhras V. Acute localised exanthematous pustulosis (ALEP) induced by clindamycin in pregnancy. Allergic contact dermatitis is the most frequent reaction associated with aminoglycosides, particularly topical neomycin for which patch testing can be useful and is validated. Aminoglycosides are classified into two main structural groups including the streptidine group consisting of streptomycin and the deoxystreptamine group consisting of gentamicin, tobramycin, neomycin, amikacin, kanamycin, plazomicin, and paromomycin [1,2,3,4,5,6] (Fig. AGEP is usually drug-induced and often related to antibiotics such as beta-lactams or macrolides. World Allergy Organ J. https://doi.org/10.1186/1939-4551-6-18, Article Delayed reactions begin later than one hour (and sometimes days) after the first dose. There have also been case reports of linezolid-associated reactions such as interstitial nephritis and DRESS [68]. Contact reaction rates for neomycin have decreased in Canada and are now similar to Europe, a trend likely influenced by the reduced availability of over-the-counter and prescription neomycin topical products in Canada [15]. Metronidazole is a nitroimidazole with structural similarities to tinidazole, clotrimazole, ketoconazole, miconazole, andalbendazole [72] (Fig. Cases of delayed allergic reaction to clindamycin have been confirmed with positive in-vitro lymphocyte transformation tests (LTTs) [43, 61]. J Investig Allergol Clin Immunol. Pseudomembranous colitis and neuropathy have also been reported. report a patient experiencing severe itching and lip swelling during a second course of oral metronidazole for Trichomonas vaginalis infection [73]. Other cutaneous manifestations like urticaria and DRESS have been reported [23, 24]. The most common adverse effect associated with clindamycin is diarrhea. Acute generalized exanthematous pustulosis induced by clindamycin. FOIA Careers, Unable to load your collection due to an error. Given the high likelihood of false negative results on patch testing, careful monitoring is required when reintroducing the antibiotic since patch testing might not be enough to confirm absence of delayed reactions [1]. Acta Derm Venereol. Yang and Xu report a case of a patient with angioedema and urticaria 12h after initiation of linezolid for an Enterococcus faecium infection [66]. Retrieved from, National Center for Biotechnology Information (2020) PubChem Compound Summary for CID 8378, Neomycin. Oral clindamycin desensitization protocol for immediate hypersensitivity [62], Intervals between doses were 30min, for a total of 4.5h. Linezolid is an oxazolidinone, a heterocyclic molecule with a nitrogen and oxygen in a 5-membered ring bridged with a carbonyl group [63] (Fig. Reported concentrations utilized for antibiotic skin testing. Neomycin is one of the most common sensitizers among topical medications in general [1, 9, 10]. A small number of the case studies described positive skin testing to metronidazole correlating with patient history including positive SPT using 125mg/mL [79] and patch testing varying from concentrations of 0.5 to 50% in petrolatum [75, 77, 79, 82, 84]. There have been a few reported cases of possible anaphylaxis to aminoglycosides. Seitz CS, Brcker E, Trautmann A. There was a case of a patient with diffuse confluent non-blanching petechiae and purpura 9days after starting linezolid with a punch biopsy showing a perivascular inflammatory infiltrate without noted changes of leukocytoclastic vasculitis [67]. Kandula S, Burke WS, Goldfarb JN. Immediate hypersensitivity reactions to linezolid have been reported with symptoms including urticaria, skin flushing, and angioedema [6466]. Hypersensitivity reactions including IgE-mediated and delayed cell-mediated reactions to aminoglycosides, clindamycin, linezolid, and metronidazole are rare. Aminoglycoside hypersensitivity is relatively uncommon, and evaluation is often warranted only if there is an imminent need for treatment with this class of antibiotics, a clinical scenario most often encountered in patients with cystic fibrosis [25]. Abarro B, Seoane FJ (2009) Immediate allergic reaction due to neomycin. Terms and conditions apply. https://doi.org/10.1111/j.1600-0560.2008.01103.x, Savard S, Desmeules S, Riopel J, Agharazii M (2009) Linezolid-associated acute interstitial nephritis and drug rash with eosinophilia and systemic symptoms (DRESS) syndrome. VanCleave HZ, Sanchez AC, Lieberman JA, Ellenburg JT, Mabry WQ. For example, patch testing has demonstrated cross-reactivity betweenmetronidazoleand tinidazole [87]. 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