Antimicrobial anaphylaxis: the changing face of severe antimicrobial allergy.

OBJECTIVES: The epidemiology, clinical characteristics and outcomes of antimicrobial-associated anaphylaxis remain ill-defined. We sought to examine antimicrobial anaphylaxis with regard to: (i) the frequency of implicated antimicrobials; (ii) attributable mortality; and (iii) referral for definitive allergy assessment. METHODS: This was conducted through a national retrospective multicentre cohort study at five Australian tertiary hospitals (January 2010 to December 2015). Cases of antimicrobial anaphylaxis were identified from ICD-10 coding and adverse drug reaction committee databases. RESULTS: There were 293 participants meeting the case definition of antimicrobial anaphylaxis and 310 antimicrobial anaphylaxis episodes. Of 336 implicated antimicrobials, aminopenicillins (62/336, 18.5%) and aminocephalosporins (57/336, 17%) were implicated most frequently. ICU admission occurred in 43/310 (13.9%) episodes; however, attributable mortality was low (3/310, 1%). The rate of anaphylaxis to IV antibiotics was 3.5 (95% CI=2.9-4.3) per 100 000 DDDs and the rate of hospital-acquired anaphylaxis was 1.9 (95% CI=2.1-3.3) per 100 000 occupied bed-days. We observed overall low rates of hospital discharge documentation (222/310, 71.6%) and follow-up by specialist allergy services (73/310, 23.5%), which may compromise medication safety and antimicrobial prescribing in future. CONCLUSIONS: This study demonstrated that a high proportion of severe immediate hypersensitivity reactions presenting or acquired in Australian hospitals are secondary to aminopenicillins and aminocephalosporins. Overall rates of hospital-acquired anaphylaxis, predominantly secondary to cephalosporins, are low, and also associated with low inpatient mortality.

Medical and pathologic characteristics of fatal anaphylaxis: a Spanish nationwide 17-year series.

Forensic series on fatal anaphylaxis are scarce, probably because the diagnosis of anaphylaxis is often complex and the incidence is low. We report on the medicolegal, demographic and histopathological characteristics of a series of sudden deaths which were investigated for anaphylaxis at the Spanish National Institute of Toxicology and Forensic Sciences (INTCF) over a 17-year period (1998-2015). A total of 122 undetermined sudden deaths from a high percentage of Spanish regions (81.5% of the total population) were sent to the INTCF with anaphylaxis as the suspected cause of death for histological, biochemical, and medicolegal investigation. Two certified allergists confirmed that 46 of the 122 cases were fatal anaphylaxis. The results indicated a median age of 51 years (IQR = 29) and a male predominance (76%). The main causes of anaphylaxis were drugs (41%), hymenoptera stings (33%), and food (13%). A previous allergic event had been reported in both food anaphylaxis (67%) and drug anaphylaxis (53%). The deaths occurred in health care settings (37%), at home (22%), and outside the home (26.09%). Histopathology data were available for 40 individuals. The most frequent autopsy findings were angioedema of the upper airways (50%), pulmonary edema (47.5%), atheromatosis of coronary vessels (32.5%), and pulmonary congestion (27.5%). Our findings for fatal anaphylaxis indicated a predominance of men, older age (≥50 years) and death in a health care setting (one-third of cases). Previous episodes had occurred in two-thirds of cases of food-induced anaphylaxis and in half of the cases of drug-induced anaphylaxis.

Delayed-type hypersensitivity reactions induced by proton pump inhibitors: A clinical and in vitro T-cell reactivity study.

BACKGROUND: Proton pump inhibitors (PPIs) have been known to induce type I hypersensitivity reactions. However, severe delayed-type hypersensitivity reactions (DHR) induced by PPI, such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug rash with eosinophilia and systemic symptoms (DRESS), are rarely reported. We conducted a study of a large series of PPI-related DHR, followed up their tolerability to alternative anti-ulcer agents, and investigated the T-cell reactivity to PPI in PPI-related DHR patients. METHODS: We retrospectively analyzed patients with PPI-related DHR from multiple medical centers in Taiwan during the study period January 2003 to April 2016. We analyzed the causative PPI, clinical manifestations, organ involvement, treatment, and complications. We also followed up the potential risk of cross-hypersensitivity or tolerability to other PPI after their hypersensitivity episodes. Drug lymphocyte activation test (LAT) was conducted by measuring granulysin and interferon-γ to confirm the causalities. RESULTS: There were 69 cases of PPI-related DHR, including SJS/TEN (n=27) and DRESS (n=10). The LAT by measuring granulysin showed a sensitivity of 59.3% and specificity of 96.4%. Esomeprazole was the most commonly involved in PPI-related DHR (51%). Thirteen patients allergic to one kind of PPI could tolerate other structurally different PPI without cross-hypersensitivity reactions, whereas three patients developed cross-hypersensitivity reactions to alternative structurally similar PPI. The cross-reactivity to structurally similar PPI was also observed in LAT assay. CONCLUSIONS: PPIs have the potential to induce life-threatening DHR. In patients when PPI is necessary for treatment, switching to structurally different alternatives should be considered.

Anaesthesia, surgery, and life-threatening allergic reactions: management and outcomes in the 6th National Audit Project (NAP6).

BACKGROUND: Anaphylaxis during anaesthesia is a serious complication for patients and anaesthetists. There is little published information on management and outcomes of perioperative anaphylaxis in the UK. METHODS: The 6th National Audit Project of the Royal College of Anaesthetists (NAP6) collected and reviewed 266 reports of Grade 3-5 anaphylaxis from all UK NHS hospitals over 1 yr. Quality of management was assessed against published guidelines. RESULTS: Appropriately senior anaesthetists resuscitated all patients. Immediate management was 'good' in 46% and 'poor' in 15%. Recognition and treatment of anaphylaxis were prompt in 97% and 83% of cases, respectively. Epinephrine was administered i.v. in 76%, i.m. in 14%, both in 6%, and not at all in 11% of cases. A catecholamine infusion was administered in half of cases. Cardiac arrests (40 cases; 15%) were promptly treated but cardiac compressions were omitted in half of patients with unrecordable BP. The surgical procedure was abandoned in most cases, including 10% where surgery was urgent. Of 54% admitted to critical care, 70% were level 3, with most requiring catecholamine infusions. Ten (3.8%) patents (mostly elderly with cardiovascular disease) died from anaphylaxis. Corticosteroids and antihistamines were generally administered early. We found no clear evidence of harm or benefit from chlorphenamine. Two patients received vasopressin and one glucagon. Fluid administration was inadequate in 19% of cases. Treatment included sugammadex in 19 cases, including one when rocuronium had not been administered. Adverse sequelae (psychological, cognitive, or physical) were reported in one-third of cases. CONCLUSIONS: Management of perioperative anaphylaxis could be improved, especially with respect to administration of epinephrine, cardiac compressions, and i.v. fluid. Sequelae were common.

Anaesthesia, surgery, and life-threatening allergic reactions: epidemiology and clinical features of perioperative anaphylaxis in the 6th National Audit Project (NAP6).

BACKGROUND: Anaphylaxis during anaesthesia is a serious complication for patients and anaesthetists. METHODS: The 6th National Audit Project (NAP6) on perioperative anaphylaxis collected and reviewed 266 reports of Grades 3-5 anaphylaxis over 1 yr from all NHS hospitals in the UK. RESULTS: The estimated incidence was ≈1:10 000 anaesthetics. Case exclusion because of reporting delays or incomplete data means true incidence might be ≈70% higher. The distribution of 199 identified culprit agents included antibiotics (94), neuromuscular blocking agents (65), chlorhexidine (18), and Patent Blue dye (9). Teicoplanin comprised 12% of antibiotic exposures, but caused 38% of antibiotic-induced anaphylaxis. Eighteen patients reacted to an antibiotic test dose. Succinylcholine-induced anaphylaxis, mainly presenting with bronchospasm, was two-fold more likely than other neuromuscular blocking agents. Atracurium-induced anaphylaxis mainly presented with hypotension. Non-depolarising neuromuscular blocking agents had similar incidences to each other. There were no reports of local anaesthetic or latex-induced anaphylaxis. The commonest presenting features were hypotension (46%), bronchospasm (18%), tachycardia (9.8%), oxygen desaturation (4.7%), bradycardia (3%), and reduced/absent capnography trace (2.3%). All patients were hypotensive during the episode. Onset was rapid for neuromuscular blocking agents and antibiotics, but delayed with chlorhexidine and Patent Blue dye. There were 10 deaths and 40 cardiac arrests. Pulseless electrical activity was the usual type of cardiac arrest, often with bradycardia. Poor outcomes were associated with increased ASA, obesity, beta blocker, and angiotensin-converting enzyme inhibitor medication. Seventy per cent of cases were reported to the hospital incident reporting system, and only 24% to Medicines and Healthcare products Regulatory Agency via the Yellow Card Scheme. CONCLUSIONS: The overall incidence of perioperative anaphylaxis was estimated to be 1 in 10 000 anaesthetics.

Consequences of avoiding ß-lactams in patients with ß-lactam allergies.

BACKGROUND: The choice of empiric antibiotics for the treatment of gram-negative bacilli (GNB) bloodstream infections (BSIs) in patients presenting with a ß-lactam (BL) allergy is often a difficult decision given that these agents are first-line treatment in many guidelines. OBJECTIVE: We sought to compare rates of clinical failure between patients with a history of BL allergy who received either a BL or a non-ß-lactam (NBL). METHODS: Adult patients with a past medical history of BL allergy and receipt of antibiotics for treatment of a GNB BSI were included from 3 academic medical centers. Treatment groups were classified as BL or NBL groups based on the empiric antibiotics received. Clinical failure was assessed 72 to 96 hours after initiation of empiric antibiotics. Hypersensitivity reactions during receipt of antibiotic therapy for the index BSI were recorded. RESULTS: A total of 552 patients were included for analysis: 433 patients in the BL group and 119 patients in the NBL group. Clinical failure was higher in the NBL group compared with the BL group (38.7% vs 27.4%, P = .030). The most common cause of clinical failure was a temperature of greater than 38.0°C 72 to 96 hours after receipt of empiric antibiotics (NBL group: 22.7% vs BL group: 13.9%, P = .016). Hypersensitivity occurred in 16 (2.9%) of 552 patients. Thirteen (2.5%) of 552 patients experiencing hypersensitivity reactions were exposed to a BL during treatment for GNB BSI. CONCLUSION: Among patients with a BL allergy, use of BL antibiotics is associated with a lower rate of clinical failure. The low rate of hypersensitivity provides further evidence about the risk of cross-reactivity between BL classes. These results support the practice of using a BL from an alternative class for patients in need of gram-negative antibiotic coverage.

Epidemiology of drug-induced anaphylaxis in a tertiary hospital in Korea.

BACKGROUND: Epidemiology and risk factors of drug-induced anaphylaxis are difficult to estimate due to lack of confirmative diagnosis and under reporting. Here we report the current state of drug-induced anaphylaxis in Korea based on an in-hospital pharmacovigilance database in a tertiary hospital. METHODS: This study is a retrospective analysis of drug-induced anaphylaxis, reported to an in-hospital pharmacovigilance center in Seoul National University Hospital from June 2009 to May 2013. Anaphylaxis occurred in patients under 18 years of age or developed by medications administered from outside pharmacies or hospitals were excluded. We assessed causative drug, incidence per use of each drug and risk factors of fatal anaphylactic shock. RESULTS: A total of 152 in-hospital drug-induced anaphylaxis cases were reported during the study period. The single most frequently reported drug was platinum compound and the incidence of anaphylaxis and anaphylactic shock in platinum compounds users was 2.84 and 1.39 per 1000 patients use. Risk factors of anaphylactic shock among total anaphylaxis cases were identified as older age ≥70 years [Odd's ratio (OR), 5.86; 95% confidence interval (CI), 1.70-20.14]. The use of iodinated contrast media (OR, 6.19; 95% CI, 1.87-20.53) and aminosteroid neuromuscular blocking agent (NMBA) (OR, 12.82; 95% CI, 1.50-109.92) were also a risk factor for the development of anaphylactic shock. CONCLUSIONS: Platinum compounds are the most commonly reported causative agents of in-hospital drug-induced anaphylaxis. Older age ≥70 years and drugs such as iodinated contrast media and aminosteroid NMBA are related with high risk of anaphylactic shock.

Oxaliplatin is a safe alternative option for patients with recurrent gynecologic cancers after hypersensitivity reaction to Carboplatin.

OBJECTIVE: The aim of this study was to determine the tolerability and efficacy of oxaliplatin in patients with recurrent gynecologic malignancies after carboplatin hypersensitivity reactions in comparison with conventionally used cisplatin. METHODS: Forty-six patients were treated with platinum-based chemotherapy from 2006 to 2011 and developed hypersensitivity reactions to carboplatin. Oxaliplatin was administered to 27 patients; 19 patients received cisplatin. Clinicopathologic variables, toxicity, and time-to-failure were analyzed retrospectively using descriptive statistics, Fisher exact, and independent sample permutation t tests. RESULTS: The median number of carboplatin cycles and cumulative dose before reaction were similar in the oxaliplatin and cisplatin groups, respectively (6 vs 7.5 cycles, P = 0.93; 980 [662] mg vs 686 [579.6] mg, P = 0.49). Non-life-threatening hypersensitivity reaction to oxaliplatin developed in 2 of 27 patients. No reactions to cisplatin occurred. The median number of oxaliplatin/cisplatin cycles was 6 in both groups. Complete response to therapy was 34.6% (oxaliplatin) and 31.6% (cisplatin); stable disease was seen in 50.0% and 36.8% of oxaliplatin- and cisplatin-treated patients, respectively (P = 0.46). Exposure to oxaliplatin resulted in less neurotoxicity than cisplatin (25.9% vs 68.4%, P = 0.01). The median number of prior chemotherapy lines in both groups was 2. The median time-to-failure was 10.8 months in oxaliplatin group and 9.8 months in cisplatin group (P = 0.86). CONCLUSIONS: Salvage therapy with oxaliplatin after hypersensitivity reaction to carboplatin is associated with excellent tolerability and time-to-failure comparable to cisplatin. When further administration of carboplatin is precluded, oxaliplatin represents a safe and effective treatment strategy in the platinum-sensitive relapse setting. The significantly lower neurotoxicity profile makes it an attractive alternative to cisplatin.

[Analysis of 59 Anaphylactic Death Cases].

OBJECTIVE: To analyze the cases of anaphylactic death cases and explore the standards of judicial expertise of anaphylactic death for providing evidence for judicial expertise. METHODS: Fifty-nine cases death due to allergic reaction in Shanghai were collected. And details of medical history, clinical manifestation of anaphylactic reaction and postmortem examination findings were reviewed for all cases. RESULTS: In the 59 cases, there were 58 cases died from drug allergy, including 77.6% of them were antibiotics. The rates of treating in standard hospital and illegal clinic were 37.3% and 61.0%, respectively. The allergic symptoms were dyspnea and facial cyanosis. The time from contacting allergens to death ranged from 1 min to 3 d. The concentration of total serum IgE ranged from 50 to 576.92 IU/mL. The results of clinical manifestation and pathological anatomy had obviously changes. CONCLUSION: Based on the exclusion of all other cause of death and synthetically analysis of details of cases, medical history, clinical manifestation and anatomy, the conclusion of anaphylactic death can reached. The details of cases including clinical history, exposure to allergens, and clinical manifestation play an important role in diagnosis of anaphylactic death.

Natural evolution of skin-test sensitivity in patients with IgE-mediated hypersensitivity to cephalosporins.

There are studies demonstrating that skin-test sensitivity to penicillins can decrease over time and that allergic patients may lose sensitivity if the responsible compounds are avoided. With regard to subjects with IgE-mediated hypersensitivity to cephalosporins, however, such studies are lacking. We evaluated prospectively in a 5-year follow-up 72 cephalosporin-allergic patients. After the first evaluation, patients were classified into two groups according to their patterns of allergologic-test positivity: to both penicillins and cephalosporins (group A), or only to cephalosporins (group B). Skin tests and serum-specific IgE assays were repeated 1 year later and, in case of persistent positivity, 3 and 5 years after the first allergologic examination. Seven (43.7%) of the 16 subjects of group A and 38 (67.8%) of the 56 patients of group B became negative; one was lost to follow-up. Patients of group B became negative sooner and more frequently than group A subjects.

Chemokine expression in diverse nonimmediate drug hypersensitivity reactions: focus on thymus activation-regulated chemokine, cutaneous T-cell-attracting chemokine, and interleukin-10.

BACKGROUND: Skin infiltration of different types of T lymphocytes is responsible for inflammatory profiles of nonimmediate drug hypersensitivity reactions (niDHRs). Important chemokines attracting skin-specific homing T cells include thymus activation-regulated chemokine (TARC) and cutaneous T-cell-attracting chemokine (CTACK). Interleukin-10 (IL-10) is a potent chemokine attracting CD8(+) T cells. OBJECTIVE: To investigate serum levels of TARC, CTACK, and IL-10 in patients with niDHRs and evaluate the correlation among these 3 chemokines. METHODS: Forty patients, including 19 patients with Stevens-Johnson syndrome and toxic epidermal necrolysis and 21 patients with maculopapular exanthema, and 21 healthy donors were recruited into the study. Clinical data of patients were obtained. Serum TARC, CTACK, and IL-10 levels were determined by enzyme-linked immunosorbent assay. RESULTS: Serum levels of TARC, CTACK, and IL-10 were significantly elevated in patients with niDHRs compared with those in normal controls (P < .05, P < .001, P < .001, respectively). The CTACK and IL-10 levels were significantly higher (P < .05, P < .001) in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis than in normal controls. Patients with maculopapular exanthema exhibited higher levels of TARC, CTACK, and IL-10 compared with normal controls (P < .001, P < .001, P < .05). Serum CTACK levels were positively correlated with TARC levels in all 40 patients (rs = 0.3422, P < .05). Serum CTACK levels positively correlated with detachment of body surface area in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis (rs = 0.510, P < .05). CONCLUSION: These results support a role for TARC, CTACK, and IL-10 in the pathogenesis of niDHRs for their chemotactic ability to attract different T-cell subtypes and different functional severities in niDHRs.

Safety profile of asparaginase Erwinia chrysanthemi in a large compassionate-use trial.

BACKGROUND: L-Asparaginase is an integral component of standard chemotherapy regimens for the treatment of acute lymphoblastic leukemia (ALL). Clinical hypersensitivity, a common reason for treatment discontinuation, has been reported in 10-30% of patients receiving Escherichia coli-derived asparaginase. After hypersensitivity, E. coli-derived asparaginase should be discontinued and an alternative asparaginase preparation, such as asparaginase Erwinia chrysanthemi, may be initiated. We conducted a compassionate-use study to collect additional safety information on asparaginase Erwinia chrysanthemi and to support FDA approval of the product. PROCEDURE: Patients with ALL or lymphoblastic lymphoma (LBL; N = 1368) who developed a hypersensitivity reaction (grade ≥2) to an E. coli-derived asparaginase participated in this trial. The recommended asparaginase Erwinia chrysanthemi dose was 25,000 IU/m(2) three days per week (Monday/Wednesday/Friday) for two consecutive weeks for each missed pegylated E. coli-derived asparaginase dose and 25,000 IU/m(2) for each missed nonpegylated asparaginase dose for the completion of their planned asparaginase treatment. RESULTS: Adverse event reports and/or case report forms were completed for 940 patients. The most common adverse event (AE) was hypersensitivity (13.6%). Eighteen patients (1.9%) died during the study. Most patients (77.6%) completed their planned asparaginase treatment with asparaginase Erwinia chrysanthemi. There was no apparent difference in the incidence of the most commonly reported AEs with asparaginase treatment by age, administration, or disease state. CONCLUSIONS: This study further established the safety profile of asparaginase Erwinia chrysanthemi in patients with ALL or LBL who had a hypersensitivity reaction to an E. coli-derived asparaginase.

Drug-induced anaphylaxis: a decade review of reporting to the Portuguese Pharmacovigilance Authority.

PURPOSE: Anaphylaxis is a potentially fatal systemic adverse drug reaction (ADR). It is an unpredictable and mostly dose-independent event that occurs suddenly following exposure to the causative drug. Our objective was to characterize a case series of anaphylactic reactions reported to the Portuguese Pharmacovigilance authority during the past decade. Patients' demographic data and implicated drugs were analyzed as well as the severity of the ADR and time trends. METHODS: This study was a retrospective analysis of episodes of anaphylaxis, defined according to the Second Symposium on the Definition and Management of Anaphylaxis Criteria, reported to the Portuguese Pharmacovigilance System between 1 January 2000 and 1 November 2010 RESULTS: Amongst the 16,157 ADR reported to the Portuguese Pharmacovigilance System during the 10-year study period, we found 918 (6 %) cases of anaphylaxis that met the proposed criteria. The age of the patients varied from 7 days to 91 years, with 87 cases (9 %) of anaphylaxis involving patients under 18 years of age. There was an overall female predominance (67 %), but the majority of pediatric patients were male (56 %). There was a trend toward increased reporting as the decade progressed, and 31 % (284) of all anaphylaxis cases were reported during the last 2 years of the study period. Of the anaphylaxis episodes reported, 19 % led to hospitalization and 24 (3 %) had a fatal outcome. Antibiotics were responsible for most cases (17 %) followed by nonsteroidal anti-inflammatory drugs/acetaminophen (13 %), antineoplastic/cytotoxic drugs and immune-modulators. Vaccines and radiographic contrast media were also important contributors to an anaphylactic event. CONCLUSIONS: In this series of drug-related anaphylaxis, we found that most of the reported episodes were associated with widely used drugs, such as antibiotics and analgesics. Anaphylaxis can occur at any age. The female gender was more highly represented, with the exception of pediatric patients.

Requirement for cardiac telemetry during intravenous phenytoin infusion: guideline fact or guideline fiction?

Guidelines recommend the use of cardiac telemetry when phenytoin is administered intravenously. Clinical areas where telemetry is available may not always be the most suitable place to monitor and treat these sick patients. We sought to clarify the evidence regarding the need for cardiac telemetry during intravenous infusion of phenytoin.

Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) in the liver--update 2012: a WFUMB-EFSUMB initiative in cooperation with representatives of AFSUMB, AIUM, ASUM, FLAUS and ICUS.

Initially, a set of guidelines for the use of ultrasound contrast agents was published in 2004 dealing only with liver applications. A second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver, as well as implementing some non-liver applications. Time has moved on, and the need for international guidelines on the use of CEUS in the liver has become apparent. The present document describes the third iteration of recommendations for the hepatic use of contrast enhanced ultrasound (CEUS) using contrast specific imaging techniques. This joint WFUMB-EFSUMB initiative has implicated experts from major leading ultrasound societies worldwide. These liver CEUS guidelines are simultaneously published in the official journals of both organizing federations (i.e., Ultrasound in Medicine and Biology for WFUMB and Ultraschall in der Medizin/European Journal of Ultrasound for EFSUMB). These guidelines and recommendations provide general advice on the use of all currently clinically available ultrasound contrast agents (UCA). They are intended to create standard protocols for the use and administration of UCA in liver applications on an international basis and improve the management of patients worldwide.

[Epidemiology of anaphylaxis]. / Epidemiologie der Anaphylaxie.

Anaphylaxis is the most severe manifestation of a mast cell dependent hypersensitivity reaction. Recent data on epidemiology indicate that food and drug induced anaphylaxis has increased within the last years. The epidemiological data on anaphylaxis vary throughout the world as the overall incidence and also relevant elicitors depend on different endogenous, but also exogenous factors (e.g. ICD-code, life style, comorbidities). Data from the anaphylaxis registry has shown that venom, drugs and foods are the most frequent elicitors for anaphylaxis within German-speaking countries, while the ranking of the elicitors is age-dependent. Risk factors for anaphylaxis are comorbidities like asthma or mastocytosis or other circumstances, which can increase either the relative risk or the severity. Further risk factors are age, gender and the concomitant intake of drugs like ACE inhibitors or acetylsalicylic acid but also exercise. Data on the clinical epidemiology of anaphylaxis are essential to follow up the most frequent elicitors and risk factors over time and accumulate data about diagnostic and therapeutic procedures in patients suffering from a potential fatal manifestation of an IgE-dependent disease. The anaphylaxis registry within the German-speaking area achieved to provide data of the most frequent elicitors, risk factors and the medical treatment from affected individuals to optimize the management of patients with anaphylaxis.

Fatal adverse effects of injected ceftriaxone sodium in China.

PURPOSE: The incidence of adverse reactions to ceftriaxone, which is widely used in China, has gradually increased, with an associated increase in patient fatality. An analysis of the reported data from articles published in China highlights the importance and extent of this growing public health problem. METHODS: We identified previously reported cases of adverse effects to ceftriaxone sodium by searching the Chinese Medical Text Database System for reports published between January 2002 and December 2009. The references cited in the articles were examined for additional reports. RESULTS: A total of 17 articles were identified that cited fatal adverse reactions in 22 cases. Most patients had been treated for upper respiratory tract infection and bronchitis and had no reported history of ceftriaxone allergy. Of the patients, 77% were treated with ceftriaxone without undergoing intradermal testing, and 36% were not offered any information on intradermal testing. Concomitant intravenous medications were prescribed in 7 cases, and an overdose of ceftriaxone sodium was prescribed for two patients. The delay between drug administration and the onset of adverse drug reactions occurred within 30 min in 72.7% of the patients. Of the deaths, 73% occurred on the first day of treatment. CONCLUSIONS: The fatal adverse events associated with ceftriaxone occurred because of inappropriate drug usage, drug overdoses, careless medical personnel, poor medical conditions, and possibly poor drug quality. Although some deaths may be unavoidable, the risks can be minimized by the appropriate administration of ceftriaxone and further consultation with the Chinese medical profession and research.

Dapsone hypersensitivity syndrome among leprosy patients in China.

OBJECTIVE: To Study the incidence and clinical characteristics of dapsone hypersensitivity syndrome (DHS) among MDT-treated leprosy patients from 2006 to 2009 in China. METHODS: A retrospective survey was carried out throughout China using a specially designed questionnaire. RESULTS: From 2006 to 2009, there were 63 new patients reported to have DHS with an incidence of 1.0%. Among these patients, 13 were complete types of DHS, the others were incomplete ones. The average age of patients with DHS was 38 years and the male to female ratio was 2.15. The average incubation period from taking dapsone to DHS onset was 32.8 days (2-6 weeks). There were 60 (95.2%) patients who presented with various skin lesions, 56 (88.9%) with fever, 40 (63.5%) with hepatic damage and 22 (34.9%) with lymphopathy. Seven patients died with a death rate of 11.1% among all patients with DHS. CONCLUSIONS: DHS is a serious adverse event resulted from dapsone. It can occur in a small number of new leprosy patients treated with dapsone containing regimen. Some patients may die of DHS if not taking timely and adequate management. Therefore local doctors should pay an attention to DHS among leprosy patients newly treated with the dapsone-containing MDT regimen.