Simultaneous drug-induced immune hemolytic anemia (DIIHA) caused by multiple drugs is rare. We report a case of a patient who developed DIIHA caused by 2 drugs. The patient's serum exhibited agglutination of ceftizoxime- or sulbactam-coated red blood cells (RBCs; via a drug-adsorption mechanism) and of uncoated RBCs in the presence of sulbactam (via an immune-complex mechanism). Although ceftizoxime is known to exhibit a positive reaction by an immune-complex method with or without reactivity with drug-coated RBCs, this patient's antibodies were reactive only against drug-coated RBCs. On the other hand, sulbactam, which is known to cause hemolytic anemia by nonimmunologic protein adsorption, exhibited positive reactions in tests with both drug-coated RBCs and in the presence of sulbactam. This is the first report of DIIHA due to a sulbactam-cefoperazone combination and the fourth report of DIIHA due to ceftizoxime. Owing to the patient's complicated laboratory results, DIIHA was suspected only at a late stage. We propose that for the prompt diagnosis of DIIHA, tests for all possible causative drugs should be conducted by 2 methods.
Anemia, Hemolytic/chemically induced/*diagnosis/immunology ; Anti-Bacterial Agents/*adverse effects ; Cefoperazone/*adverse effects ; Ceftizoxime/*adverse effects ; Erythrocytes/chemistry/metabolism ; Female ; Humans ; Middle Aged ; Sulbactam/*adverse effects

Ambroxol ; therapeutic use ; Anti-Bacterial Agents ; therapeutic use ; Humans ; Infant ; Male ; Penicillanic Acid ; analogs & derivatives ; therapeutic use ; Pneumonia ; drug therapy ; etiology ; virology ; Poliomyelitis ; immunology ; Vaccines ; adverse effects ; immunology

BACKGROUNDBacterial pneumonia in the recipients of liver transplantation (LTX) is a common postoperative complication influencing the prognosis greatly. In this article, the diagnosis and treatment of bacterial pneumonia in 33 LTX recipients are reported.

METHODSFrom February 1999 to January 2003, a total of 103 patients underwent allogeneic LTX at our center; afterwards, a retrospective analysis was made on their postoperative clinical manifestations, including symptoms (expectoration, panting and fever), sign (rale), results of laboratory examinations (white blood cell count and sputum culture of tracheal secretions or pleural fluid culture), and chest X-ray films. The following data of the pneumonia and non-pneumonia groups were collected, and the rank sum test (SPSS 11.0, Wilcoxon's method) was used to analyze the duration of postoperative respirator utilization and the volume of pleural effusion through pleurocentesis or pleural drainage.

RESULTSIn the 103 patients, 33 experienced 53 episodes of bacterial pneumonia during their hospital stay after transplantation, 14 of them (42.42%) had more than three manifestations of the seven mentioned above. The pathogens causing bacterial pneumonia included Pseudomonas aeruginosa (17.48%), Klebsiella pneumoniae (15.53%), Acinetobacter baumannii (10.68%), and Staphylococcus aureus (7.77%). Amilkacin, tienam, ciprofloxacin, vancomycin, etc. were the antibiotics of choice against those bacteria. Acute rejection occurred during the treatment of bacterial pneumonia in 16 patients, and 5 of them died. Wilcoxon's rank sum test of the data indicated that the pneumonia group had longer duration of postoperative ventilator treatment and larger volume of pleural effusion than the non-pneumonia group (P < 0.05).

CONCLUSIONSThe clinical manifestations of pneumonia after LTX might be atypical, and special attention should be paid to the respiratory symptoms and signs within 2 months after LTX. Whenever the diagnosis of bacterial pneumonia is confirmed, consideration should be given to reasonable use of antibiotics and regulation of immunity in addition to other routine therapies.

Adult ; Aged ; Anti-Bacterial Agents ; therapeutic use ; Female ; Humans ; Liver Transplantation ; adverse effects ; Male ; Middle Aged ; Pneumonia, Bacterial ; diagnosis ; drug therapy ; immunology ; Postoperative Complications ; diagnosis ; drug therapy ; immunology ; Retrospective Studies

Eleven cases of human brucellosis occurred among livestock workers and a veterinarian who lived and worked in a rural area around Jeongeup City, Jeollabuk-Do, Korea from February 2003 to August 2003. Eight of the patients had taken care of Korean native cattle that were infected with bovine brucellosis and had already been slaughtered. Two of the patients had taken care of dairy cattle, and one case was a veterinarian who acquired the disease through an accidental contact with infected cattle while assisting in calf delivery. Eleven cases were identified by serologic work ups and four cases were identified via positive blood cultures. This study shows that the Republic of Korea is no longer free of human brucellosis, Brucella abortus biotype 1. We reviewed the patients' characteristics and serologic data during the oneyear follow up period, and we also discuss on the efficacy and side effects of the rifampin and doxycyline regimen used for the treatment of human brucellosis.
Adult ; Animal Husbandry ; Animals ; Anti-Bacterial Agents/adverse effects/therapeutic use ; Antibodies, Bacterial/blood ; Base Sequence ; Brucella abortus/genetics/immunology/isolation and purification ; Brucellosis/drug therapy/*epidemiology/microbiology/transmission ; Brucellosis, Bovine/transmission ; Cattle ; DNA, Bacterial/genetics ; Disease Outbreaks ; Doxycycline/adverse effects/therapeutic use ; Female ; Humans ; Korea/epidemiology ; Male ; Middle Aged ; Occupational Diseases/drug therapy/epidemiology/immunology/microbiology ; Rifampin/adverse effects/therapeutic use ; Veterinarians

PURPOSE: Cefaclor is widely prescribed for various infectious diseases. As its consumption increases, the number of hypersensitivity reactions to cefaclor has increased. This study aimed to evaluate the immunologic findings of immediate hypersensitivity to cefaclor. MATERIALS AND METHODS: We enrolled 47 patients with immediate hypersensitivity to cefaclor from Ajou University Hospital and Asan Medical Center. Serum specific IgE, IgG1, and IgG4 antibodies to cefaclor-human serum albumin (HSA) conjugate were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The most common phenotype was anaphylaxis (Group I, 78.7%), followed by urticaria (Group II, 21.3%). The detection of specific IgE, IgG1, and IgG4 to cefaclor-HSA conjugate by ELISA tended to be higher in Group I (40.5%, 41.7%, 21.6%) than in Group II (20.0%, 20.0%, 0%) with no statistical significance. Significant associations were found between specific IgE and IgG1 or IgG4 (p<0.001, p=0.019). ELISA inhibition tests showed significant inhibitions by both free cefaclor and cefaclor-HSA conjugate. For basophil activation tests in patients having no specific IgE antibody, the CD63 expression level on basophils increased with incubations of free cefaclor. CONCLUSION: The most common manifestation of immediate hypersensitivity to cefaclor was anaphylaxis, most of which was mediated by IgE; however, a non-IgE mediated direct basophil activation mechanism was suggested in a subset of anaphylaxis patients.
Adolescent ; Adult ; Aged ; Anaphylaxis/*chemically induced/immunology ; Anti-Bacterial Agents/adverse effects/*immunology ; Antigens, CD63 ; Basophils/metabolism ; Cefaclor/*adverse effects/immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Hypersensitivity, Immediate/chemically induced/diagnosis/*immunology ; Immunoglobulin E/*blood ; Immunoglobulin G/immunology ; Male ; Middle Aged ; Retrospective Studies ; Skin Tests ; Urticaria/chemically induced/diagnosis/immunology ; Young Adult

BACKGROUND/AIMS: Antibiotic skin testing is a useful procedure for identifying patients with IgE-mediated hypersensitivity to antibiotics. The procedures, however, have not been standardized, and the testing is performed with diverse protocols in Korean hospitals wards. Thus, we examined the current practice of antibiotic skin testing in Korea. METHODS: We sent questionnaires to 12 allergists working in secondary or tertiary referral hospitals and collected them by e-mail or fax. The questionnaire included items such as the types and concentrations of the tested antibiotics, the methods of antibiotic skin testing, and the interpretation of the results. RESULTS: All hospitals responded to the questionnaire. The antibiotic skin testing protocols were variable, inconsistent, and differed with regard to the type and concentrations of antibiotics, the volume injected, and the interpretation of the results. Moreover, the protocols differed from the commonly recommended procedures in the medical literature. CONCLUSIONS: Standardized guidelines for antibiotic skin testing are needed for the safe and effective use of antibiotics in Korea.
Allergy and Immunology/*statistics & numerical data ; Anti-Bacterial Agents/*adverse effects ; Drug Hypersensitivity/*diagnosis ; *Health Care Surveys ; Humans ; Medical Staff, Hospital/statistics & numerical data ; Professional Practice/statistics & numerical data ; Questionnaires ; Republic of Korea ; Skin Tests/*utilization

OBJECTIVEOver the past several decades, there has been a significant increase in allergy and asthma in the world, which correlates with alterations in microflora and widespread use of antibiotics. The authors have developed a mouse model of antibiotics-induced microbiota disruption. In that model, mice were challenged by intranasal exposure to Aspergillus fumigatus allergens to explore the relation of allergic airway response and intestinal microflora disruption.

METHODSSixty female BALB/c mice were divided at random into 6 groups with 10 mice in each. (1) First antibiotic therapy group: the mice were given oral cefoperazone for 7 days, on day 7, mice were inoculated with Candida albicans (10(9)/ml, 50 microl) orally. (2) First control group: the mice were treated as first antibiotic therapy group, but cefoperazone and Candida albicans were replaced by saline. The mice in groups (1) and (2) were sacrificed on day 8, and cecal contents were collected for quantitative analysis of the intestinal bacterial flora. (3) Antibiotic therapy and challenge group: the mice were treated as the first antibiotic therapy group, then challenged (day 9 and 16) by intranasal exposure to Aspergillus fumigatus allergen. (4) Second antibiotic therapy group: the mice were treated as the first antibiotic therapy group, then challenged (day 9 and 16) by intranasal exposure to saline. (5) Challenge group: the mice were treated as the first control group, then challenged (day 9 and 16) by intranasal exposure to Aspergillus fumigatus allergen. (6) Second control group: the mice were treated as the first control group, then challenged (day 9 and 16) by intranasal exposure to saline. The mice in (3) - (6) group were killed for analysis of allergic airway response on day 19.

RESULTSThe quantity of Enterobacteriaceae, Enterococcus, Bifidobacterium and Lactobacillus in first antibiotic therapy group was significantly lower than that in the first control group, the quantity of Candida albicans increased in the first antibiotic therapy group as compared with the first control group. Mice intestinal microflora were disrupted with weight reduction and increased moisture in feces. After challenging with Aspergillus fumigatus allergens via intranasal inhalation, the total cell count, eosinophils, lymphocytes and neutrophils increased in BALF, especially in bronchoalveolar lavage fluid (BALF) from the mice in antibiotic therapy and challenge groups. IL-4 level in BALF from antibiotic therapy and challenge group (45.35 +/- 2.36) pg/ml was higher than that in the second control group (35.32 +/- 2.53) pg/ml. The expression of GATA-3 mRNA in the mice lung tissue (0.569 +/- 0.023) was higher than that in the second control group (0.410 +/- 0.020), and the ratios of T-bet/GATA-3 (0.578 +/- 0.021) decreased as compared with that in the second control group (0.804 +/- 0.035). IFN-gamma level in BALF from any group was not significantly different. In the absence of antibiotics, mice exposed to Aspergillus fumigatus allergen did not develop an allergic response in the airways.

CONCLUSIONSThe allergic (Th2) immune response can be induced by airway challenge with Aspergillus fumigatus allergen in the mice in which the intestinal microflora disruption resulted from antibiotic therapy, this result suggests that the intestinal microflora disruption resulted from antibiotic therapy is a risk factor for allergy and asthma.

Animals ; Anti-Bacterial Agents ; adverse effects ; Antibiosis ; Aspergillus fumigatus ; chemistry ; growth & development ; Asthma ; drug therapy ; microbiology ; Bronchoalveolar Lavage Fluid ; microbiology ; Cefoperazone ; therapeutic use ; Disease Models, Animal ; Eosinophils ; drug effects ; microbiology ; Female ; Hypersensitivity ; drug therapy ; microbiology ; Hypersensitivity, Immediate ; microbiology ; Intestines ; drug effects ; microbiology ; physiopathology ; Lung ; drug effects ; microbiology ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; adverse effects ; immunology ; Respiratory System ; microbiology

INTRODUCTIONDue to lifelong immunosuppression, renal transplant recipients (RTRs) are at risk of infectious complications such as pneumonia. Severe pneumonia results in respiratory failure and is life‑threatening. We aimed to examine the influence of immunosuppressant dose reduction on RTRs with bacterial pneumonia and respiratory failure.

METHODSFrom January 2001 to January 2011, 33 of 1,146 RTRs at a single centre developed bacterial pneumonia with respiratory failure. All patients were treated using mechanical ventilation and aggressive therapies in the intensive care unit.

RESULTSAverage time from kidney transplantation to pneumonia with respiratory failure was 6.8 years. In-hospital mortality rate was 45.5% despite intensive care and aggressive therapies. Logistic regression analysis indicated that a high serum creatinine level at the time of admission to the intensive care unit (odds ratio 1.77 per mg/dL, 95% confidence interval 1.01-3.09; p = 0.045) was a mortality determinant. Out of the 33 patients, immunosuppressive agents were reduced in 17 (51.5%). We found that although immunosuppressant dose reduction tended to improve in-hospital mortality, this was not statistically significant. Nevertheless, during a mean follow-up period of two years, none of the survivors (n = 18) developed acute rejection or allograft necrosis.

CONCLUSIONIn RTRs with bacterial pneumonia and respiratory failure, higher serum creatinine levels were a mortality determinant. Although temporary immunosuppressant dose reduction might not reduce mortality, it was associated with a minimal risk of acute rejection during the two-year follow-up. Our results suggest that early immunosuppressant reduction in RTRs with severe pneumonia of indeterminate microbiology may be safe even when pathogens are bacterial in nature.

Adult ; Aged ; Anti-Bacterial Agents ; therapeutic use ; Bacterial Infections ; complications ; Comorbidity ; Creatinine ; blood ; Female ; Graft Rejection ; Hospital Mortality ; Humans ; Immunosuppression ; adverse effects ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Intensive Care Units ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Pneumonia ; complications ; microbiology ; Renal Insufficiency ; complications ; immunology ; surgery ; Respiratory Insufficiency ; complications ; Retrospective Studies ; Risk Factors

PURPOSE: Cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 play a key role in the pathogenesis of in-stent restenosis. We investigated the effect of a short-term therapy of celecoxib, a COX-2 inhibitor, with or without doxycycline, an MMP inhibitor, after coronary stenting on inflammatory biomarkers and neointimal hyperplasia. MATERIALS AND METHODS: A total of 75 patients (86 lesions) treated with bare metal stents were randomized into three groups: 1) combination therapy (200 mg celecoxib and 20 mg doxycycline, both twice daily), 2) celecoxib (200 mg twice daily) only, and 3) non-therapy control. Celecoxib and doxycycline were administered for 3 weeks after coronary stenting. The primary endpoint was neointimal volume obstruction by intravascular ultrasound (IVUS) at 6 months. The secondary endpoints included clinical outcomes, angiographic data, and changes in blood levels of inflammatory biomarkers. RESULTS: Follow-up IVUS revealed no significant difference in the neointimal volume obstruction among the three treatment groups. There was no difference in cardiac deaths, myocardial infarctions, target lesion revascularization or stent thrombosis among the groups. Blood levels of high-sensitivity C-reactive protein, soluble CD40 ligand, and MMP-9 varied widely 48 hours and 3 weeks after coronary stenting, however, they did not show any significant difference among the groups. CONCLUSION: Our study failed to demonstrate any beneficial effects of the short-term therapy with celecoxib and doxycycline or with celecoxib alone in the suppression of inflammatory biomarkers or in the inhibition of neointimal hyperplasia. Large scale randomized trials are necessary to define the role of anti-inflammatory therapy in the inhibition of neointimal hyperplasia.
Aged ; Angioplasty, Balloon, Coronary ; Anti-Bacterial Agents/therapeutic use ; Biological Markers/metabolism ; Coronary Artery Disease/immunology/metabolism/*therapy ; Cyclooxygenase 2 Inhibitors/therapeutic use ; Doxycycline/*therapeutic use ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Humans ; Male ; Metals ; Middle Aged ; Neointima/*drug therapy/*immunology/metabolism ; Pyrazoles/*therapeutic use ; Stents/*adverse effects ; Sulfonamides/*therapeutic use