Desensitization to antibiotics in children.

Drug hypersensitivity reactions can occur to almost all drugs and antibiotics are among the most common cause for this kind of reactions. Drug hypersensitivity may affect any organ or system, and manifestations range widely in clinical severity from mild pruritus to anaphylaxis. In most cases, the suspected drug is avoided in the future. In case of infection, there is usually a safe antibiotic alternative. Nonetheless, in some cases, no alternative treatment exists for optimal therapy. Under these circumstances, desensitization may be performed. Drug desensitization is defined as the induction of a temporary state of tolerance to a drug which can only be maintained by continuous administration of the medication responsible for the hypersensitivity reaction. Desensitization is mainly performed in IgE-mediated reactions. Increasing doses of the implicated drug are administered over a short period of time, until the therapeutic dose is achieved and tolerated. Very few studies confined to children are found in literature. Most of them are case reports. In general, the proposed desensitization schemes are similar to those used in adults differing only in the final dose administered. The purpose of this study is to review desensitization to antibiotics in children presenting and discussing three clinical practical cases of desensitization in this age group.

Immediate allergic reactions to cephalosporins: cross-reactivity and selective responses.

BACKGROUND: After penicillins, cephalosporins are the most important beta-lactams inducing IgE-mediated reactions. Responses may be selective or cross-reactive with common beta-lactam determinants. Unlike determinants derived from benzylpenicillin, cephalosporin allergenic determinants have not been properly identified, even though a wide variety of these beta-lactams is currently used. OBJECTIVE: We sought to evaluate the IgE response in subjects with immediate allergic reactions to injectable cephalosporins and to assess their reactivity to different penicillins and cephalosporins. METHODS: We studied 30 subjects with immediate reactions to one or more of the following cephalosporins: ceftriaxone, cefotaxime, ceftazidime, and cefuroxime. Skin tests and in vitro-specific IgE antibody assays were performed for major and minor determinants of penicillin G, amoxicillin, and ampicillin, as well as for the culprit cephalosporins. Responses to cephalosporins other than the culprit ones were also studied by using skin testing. RESULTS: Twenty-six patients (group A, 86.7%) displayed skin test and RAST negativity to penicillin determinants and skin test positivity to cephalosporins, with RAST confirmation in 9 patients. Four subjects (group B, 13.3%) had a positive response to penicillin determinants. In group A two patterns of reactivity were observed: one characterized by a response only to the culprit cephalosporin (n = 15, 57.7%) and the other by positive responses to different cephalosporins, including the responsible cephalosporins (n = 11, 42. 3%). CONCLUSION: Most patients with a history of immediate reactions to cephalosporins are sensitized to determinants generated only by cephalosporins (group A), although a small percentage react to penicillin determinants (group B). Some patients from group A responded only to the culprit cephalosporin, but others reacted to different cephalosporins. These findings can be explained in terms of either selective response to unique determinants or cross-reactivity.

Prevalence of Bacterial Pathogens and Susceptibility Patterns from clinical sources in Trinidad

During a 12-month period (January-December, 1997), bacterial isolates of specimens from in-patients and out-patients of the Eric Wiliams Sciences Complex (EWMSC) were reviewed. A total of 3,513 specimens were processed, 43.1 percent from in-patients and 56.9 percent from out-patients. Of the 3,513 specimens, 1,129 (32.1 percent) yielded positive cultures. Micro-organisms from wounds, sputum and genital tract accounted for 90.2 percent, 51.5 percent and 31.8 percent, respectively, of all isolates. E coli (17.4 percent) and Enterococci (12.2percent) were the predominant isolates and were also the major pathogens from blood stream infections, 25.8 percent and 18.2 percent, respectively, followed by P aeruginosa, 15.2 percent. High levels of resistance were seen to ampicillin, augmentin (amoxicillin-clavulanic acid) and tetracycline. The most effective antibiotics were ceftazidime (no resistance in E coli Citrobacter spp, non-typhoidal Salmonella and Group B streptococci, 63.2 percent resistance in Acinetobacter spp, 15.2 percent in Enterobacter spp, 17.4 percent in Klebsiella spp.], erythromycin (no resistance in Enterobacter and Citrobacter spp, and 89.5 percent in Acinetobacter (spp), erythromycin (no resistance in Groups A and B streptococci, 85.1 percent in S aurens and S pneumoniae). The spectrum of isolates will provide clinicians with data on which to base their "best guess" aetiologic agent and choice of antibiotics when faced with infectious diseases in areas where laboratory assistance is not readily available.(Au)

Prevalence of Bacterial Pathogens and Susceptibility Patterns from clinical sources in Trinidad

During a 12-month period (January-December, 1997), bacterial isolates of specimens from in-patients and out-patients of the Eric Wiliams Sciences Complex (EWMSC) were reviewed. A total of 3,513 specimens were processed, 43.1 percent from in-patients and 56.9 percent from out-patients. Of the 3,513 specimens, 1,129 (32.1 percent) yielded positive cultures. Micro-organisms from wounds, sputum and genital tract accounted for 90.2 percent, 51.5 percent and 31.8 percent, respectively, of all isolates. E coli (17.4 percent) and Enterococci (12.2percent) were the predominant isolates and were also the major pathogens from blood stream infections, 25.8 percent and 18.2 percent, respectively, followed by P aeruginosa, 15.2 percent. High levels of resistance were seen to ampicillin, augmentin (amoxicillin-clavulanic acid) and tetracycline. The most effective antibiotics were ceftazidime (no resistance in E coli Citrobacter spp, non-typhoidal Salmonella and Group B streptococci, 63.2 percent resistance in Acinetobacter spp, 15.2 percent in Enterobacter spp, 17.4 percent in Klebsiella spp.], erythromycin (no resistance in Enterobacter and Citrobacter spp, and 89.5 percent in Acinetobacter (spp), erythromycin (no resistance in Groups A and B streptococci, 85.1 percent in S aurens and S pneumoniae). The spectrum of isolates will provide clinicians with data on which to base their "best guess" aetiologic agent and choice of antibiotics when faced with infectious diseases in areas where laboratory assistance is not readily available.

An assessment of antigenic potential of beta-lactam antibiotics, low molecular weight drugs, using guinea pig models.

Allergic reactions are among the common adverse effects in humans. However, it is widely assumed that there are practically no reliable animal models for preclinical tests of low-molecular weight drugs that are available to predict such reactions. This study was designed to compare the detecting ability of test methods for antigenic potential of eight beta-lactam antibiotics with which allergic outcome has been reported in humans. The tests included active systemic anaphylaxis (ASA), delayed type skin reaction (DSR), maximization test (GPMT) in guinea pigs sensitized with antibiotics emulsified with Freund's complete adjuvant, passive cutaneous anaphylaxis (PCA) and enzyme-linked immunosorbent assay (ELISA) as serological tests. PCA and ELISA though using protein-conjugates as detecting antigens, especially ELISA, showed positive reactions with relatively high incidence. On the other hand, GPMT was the most sensitive method to detect antigenic potential of antibiotics despite the use of antibiotics alone for sensitizing and challenging phases. It is suggested that GPMT can be considered the most reliable method in preclinical testing.

Sensitization to aztreonam and cross-reactivity with other beta-lactam antibiotics in high-risk patients with cystic fibrosis.

The immunogenicity, allergenicity, and cross-reactivity of aztreonam were investigated in 21 patients with cystic fibrosis (CF) (aged 5 to 39 years) with well-documented histories of allergic systemic reactions (SRs) to penicillin and/or cephalosporin antipseudomonal beta-lactam antibiotics (BLAs). Skin tests (STs) with penicilloyl-polylysine (PPL), penicillin minor determinant mixture, and antipseudomonal BLA were positive in 19 patients (90%). The BLA causing the most recent allergic reaction, minor determinant mixture, or PPL, was positive in 89%, 53%, and 32% of ST-positive patients, respectively. Serum PPL-specific IgE antibodies were not detectable, although PPL-specific IgG antibodies were found in 64% of patients tested. STs to aztreonam reagents were performed and were initially negative in 20 patients. One patient was ST positive to the polylysine conjugate of hydrolyzed aztreonam (SQ 27629), despite no prior exposure to aztreonam, and was not treated. Of 20 patients treated with aztreonam, four were demonstrated to be sensitized by exposure (one had an SR during initial treatment course, two had SRs on reexposure, and one patient was asymptomatic after intravenous desensitization) by positive aztreonam reagent skin responses on repeat testing. Aztreonyl-specific IgE and IgG serum antibodies were not detected in any patients, including patients with allergic reactions to aztreonam. Thus, aztreonam is generally well tolerated in high-risk patients with CF allergic to other BLAs and appears to have reduced immunogenicity by serologic testing. However, caution should be exercised with aztreonam in BLA-allergic patients with CF in light of 5% preexisting ST cross-reactivity and 20% sensitization rates found in this study.