Drug-induced immune hemolytic anemia (DIIHA) is a rare side effect of drugs. DIIHA may cause a systemic inflammatory response that results in acute multi-organ failure and death. Ceftizoxime belongs to the class of third generation cephalosporins, which are the most common drugs associated with DIIHA. Herein, we present a case of a 66-year-old man who developed fatal DIIHA after receiving a second dose of ceftizoxime. He was admitted to receive photodynamic therapy. He had a history of a single parenteral dose of ceftizoxime 3 months prior to admission. On the day of the procedure — shortly after the infusion of ceftizoxime — the patient's mental status was altered. The blood test results revealed hemolysis. Oliguric acute kidney injury developed, and continuous renal replacement therapy had to be applied. On the suspicion of DIIHA, the patient underwent plasmapheresis. Diagnosis was confirmed by a detection of drug-dependent antibody with immune complex formation. Although his hemolysis improved, his liver failure did not improve. He was eventually discharged to palliative care, and subsequently died.
Acute Kidney Injury ; Aged ; Anemia, Hemolytic* ; Antigen-Antibody Complex ; Ceftizoxime ; Cephalosporins ; Diagnosis ; Hematologic Tests ; Hemolysis ; Humans ; Liver Failure ; Palliative Care ; Photochemotherapy ; Plasmapheresis ; Renal Replacement Therapy

Drug-induced immune hemolytic anemia (DIIHA) is a rare side effect of drugs. DIIHA may cause a systemic inflammatory response that results in acute multi-organ failure and death. Ceftizoxime belongs to the class of third generation cephalosporins, which are the most common drugs associated with DIIHA. Herein, we present a case of a 66-year-old man who developed fatal DIIHA after receiving a second dose of ceftizoxime. He was admitted to receive photodynamic therapy. He had a history of a single parenteral dose of ceftizoxime 3 months prior to admission. On the day of the procedure — shortly after the infusion of ceftizoxime — the patient's mental status was altered. The blood test results revealed hemolysis. Oliguric acute kidney injury developed, and continuous renal replacement therapy had to be applied. On the suspicion of DIIHA, the patient underwent plasmapheresis. Diagnosis was confirmed by a detection of drug-dependent antibody with immune complex formation. Although his hemolysis improved, his liver failure did not improve. He was eventually discharged to palliative care, and subsequently died.
Acute Kidney Injury ; Aged ; Anemia, Hemolytic ; Antigen-Antibody Complex ; Ceftizoxime ; Cephalosporins ; Diagnosis ; Hematologic Tests ; Hemolysis ; Humans ; Liver Failure ; Palliative Care ; Photochemotherapy ; Plasmapheresis ; Renal Replacement Therapy

INTRODUCTIONIncreasing resistance in Escherichia coli and Klebsiella pneumoniae to firstline antibiotics makes therapeutic options for urinary tract infections (UTIs) challenging. This study investigated the in vitro efficacies of 6 antibiotics against multidrug resistant (MDR) uropathogens.

MATERIALS AND METHODSMinimum inhibitory concentrations to ceftibuten, cefpodoxime, fosfomycin, mecillinam, temocillin, and trimethoprim were determined against 155 MDR-isolates of E. coli and K. pneumoniae. The presence of extended-spectrum beta-lactamases (ESBL) and plasmid-borne AmpC enzymes was determined by phenotypic testing with genotyping performed by multiplex polymerase chain reaction.

RESULTSTemocillin demonstrated highest susceptibility rates for both E. coli (95%) and K. pneumoniae (95%) when breakpoints for uncomplicated UTIs were applied; however, temocillin susceptibility was substantially lower when "systemic infection" breakpoints were used. Fosfomycin demonstrated the best in vitro efficacy of the orally available agents, with 78% and 69% of E. coli and K. pneumoniae isolates susceptible, respectively. The next most effective antibiotics were ceftibuten (45%) and mecillinam (32%). ESBL and ampC genes were present in 47 (30%) and 59 (38%) isolates.

CONCLUSIONThis study demonstrated few oral therapeutic options for MDR-uropathogens, with fosfomycin demonstrating the best in vitro activity.

Amdinocillin ; pharmacology ; Anti-Bacterial Agents ; pharmacology ; Bacterial Proteins ; genetics ; Ceftizoxime ; analogs & derivatives ; pharmacology ; Cephalosporins ; pharmacology ; Drug Resistance, Multiple, Bacterial ; genetics ; Escherichia coli ; drug effects ; genetics ; Escherichia coli Infections ; microbiology ; Fosfomycin ; pharmacology ; Genotype ; Humans ; In Vitro Techniques ; Klebsiella Infections ; microbiology ; Klebsiella pneumoniae ; drug effects ; genetics ; Microbial Sensitivity Tests ; Multiplex Polymerase Chain Reaction ; Penicillins ; pharmacology ; Singapore ; Trimethoprim ; pharmacology ; Urinary Tract Infections ; microbiology ; beta-Lactamases ; genetics

The HACEK group of microorganisms is responsible for approximately 3-6% of endocarditis cases and is a major cause of culture-negative endocarditis. Here, we report a case of Haemophilus parainfluenzae infective endocarditis that was diagnosed by direct PCR sequencing of 16S rRNA from resected vegetation. A healthy 26-yr-old man was admitted to the emergency room (ER) on March 27, 2011 because of intermittent high fever. The patient was prescribed cefpodoxime for 5 days at the ER. Six and 11 sets of blood cultures were performed at the ER and in a general ward, respectively, using BACTEC Plus Aerobic/F (Becton-Dickinson, USA) and Lytic Anaerobic/F Plus (BD) together. Echocardiography revealed a large vegetation at the posterior mitral valve leaflet. After performing mitral valvoplasty on hospital day (HD) 11, the vegetation tissue was cultured in thioglycolate broth, blood agar, Brucella agar, and MacConkey agar for 7 days, but no organism was grown. Direct PCR sequencing of 16S rRNA of the tissue revealed the presence of H. parainfluenzae. In the 17 sets of blood cultures, bacterial growth was detected in only 2 aerobic bottles of 5 sets taken at HD 9 after 10-day and 14-day incubation. The organism was identified as H. parainfluenzae by using the VITEK NHI card (bioMerieux, France). Direct PCR sequencing of vegetation could be useful in diagnosing bacterial pathogens in infective endocarditis patients, especially in culture-negative cases.
Agar ; Brucella ; Ceftizoxime ; Echocardiography ; Emergencies ; Endocarditis ; Fever ; Haemophilus ; Haemophilus parainfluenzae ; Humans ; Mitral Valve ; Paramyxoviridae Infections ; Patients' Rooms ; Polymerase Chain Reaction ; Sequence Analysis, RNA

PURPOSE: Cephalosporins can induce occupational allergies, such as asthma, urticaria, and anaphylaxis. We investigated the prevalence and risk factors of sensitization to cephalosporin. METHODS: A total of 161 health care workers (HCW), including 138 nurses and 23 pharmacists, and 86 unexposed non-atopic healthy controls were recruited from a single tertiary hospital and the general population. A questionnaire regarding work-related symptoms was administered along with skin prick tests (SPT) to the three most commonly used cephalosporins (cefotiam, ceftriaxone, and ceftizoxime). Serum specific IgE antibodies to conjugates of the three cephalosporins and human serum albumin (HSA) were measured by enzyme-linked immunosorbent assay (ELISA). Binding specificities were confirmed by ELISA inhibition tests. RESULTS: The prevalence of work-related symptoms in association with cephalosporins was 17.4%. The sensitization rate to any cephalosporin was 3.1% by SPT. Sensitization rates determined by measurement of serum specific IgE antibodies were 17.4% for any cephalosporin, 10.4% for cefotiam, 6.8% for ceftriaxone, and 3.7% for ceftizoxime. A personal history of any antibiotic allergy was a risk factor for work-related symptoms (OR, 24.93; 95% CI, 2.61-238), but not for the presence of serum specific IgE antibodies to cephalosporins (OR, 0.9; 95% CI, 0.18-4.53). A personal history of atopic dermatitis was a risk factor for the presence of serum specific IgE antibodies to cefotiam-HSA conjugate (OR, 6.30; 95% CI, 1.23-32.3). CONCLUSIONS: A high cephalosporin sensitization rate (17.4%) was detected by ELISA in HCW exposed to cephalosporins. Monitoring of serum specific IgEs to cephalosporin-HSA conjugates will be useful for detecting sensitized subjects.
Anaphylaxis ; Antibodies ; Asthma ; Cefotiam ; Ceftizoxime ; Ceftriaxone ; Cephalosporins ; Delivery of Health Care ; Dermatitis, Atopic ; Enzyme-Linked Immunosorbent Assay ; Humans ; Hypersensitivity ; Immunoglobulin E ; Occupational Diseases ; Pharmacists ; Prevalence ; Risk Factors ; Serum Albumin ; Skin ; Tertiary Care Centers ; Urticaria ; Surveys and Questionnaires

A novel qualitative analytical method by using two-dimensional chromatographic correlation spectroscopy techniques for recognizing impurity peaks of HPLC methods of quality control and LC-MS chromatographic system was established. The structures of major degradation products of ceftizoxime and cefdinir were identified by LC-MS and MassWorks application; the standard chromatographic and spectral data of the degradation impurities were obtained by high-performance liquid chromatography with diode array detection. The impurity peaks of two-dimensional chromatography were matched by comparison of spectra and calculating correlation coefficients. Peaks in chromatography can be identified accurately and rapidly in different chromatographic systems such as column and mobile phase changed. The method provides a new way and thought to identify the peaks in quality control of impurities without reference impurity substances.
Ceftizoxime ; analysis ; chemistry ; Cephalosporins ; analysis ; chemistry ; Chromatography, High Pressure Liquid ; methods ; Chromatography, Liquid ; methods ; Drug Contamination ; Mass Spectrometry ; methods ; Quality Control

Burkholderia cepacia (B. cepacia) infection is rarely reported in an immunocompetent host. It is a well known occurence in patients with cystic fibrosis and chronic granulomatous disease where it increases both morbidity and mortality. It has also been included in the list of organisms causing nosocomial infections in an immunocompetent host, most of them transmitted from the immunocompromised patient in which this organism harbors. We report a rare case of isolation of B. cepacia from the bronchoalveolar lavage fluid of an immunocompetent agriculturist who presented with productive cough and fever associated with a pyopneumothorax. This is the first case of community acquired infection reported in an immunocompetent person in India.
Adult ; Anti-Bacterial Agents ; therapeutic use ; Azithromycin ; therapeutic use ; Bronchoalveolar Lavage Fluid ; microbiology ; Burkholderia Infections ; diagnosis ; drug therapy ; transmission ; Burkholderia cepacia ; drug effects ; isolation & purification ; Ceftazidime ; therapeutic use ; Ceftizoxime ; therapeutic use ; Community-Acquired Infections ; diagnosis ; drug therapy ; Drug Resistance, Multiple, Bacterial ; Humans ; Immunocompetence ; India ; Male ; Pneumothorax ; complications

PURPOSE: Skin allergies through type 1 and 4 hypersensitivity reactions are the most frequent manifestations of drug allergies. We had previously experienced a case of a nurse with cefotiam-induced contact urticaria syndrome. To aid in preventing the progression of drug-induced allergic disease in nurses, we conducted a survey of tertiary hospital nurses who were likely to have been exposed professionally to antibiotics. METHODS: All 539 staff nurses at a tertiary hospital were asked to respond to a questionnaire regarding antibiotic exposure. Of the 457 nurses (84.8%) who responded, 427 (79.2%) received a physical examination of the hands and 318 (59.0%) received skin prick tests with the beta-lactam antibiotics cefotiam, cefoperazone, ceftizoxime, flomoxef, piperacillin and penicillin G. RESULTS: A positive response to at least one of the antibiotics occurred in 8 (2.6%) of the 311 subjects included in the analysis and stages 1 and 2 contact urticaria syndrome were observed in 38 (8.9%) and 3 (0.7%) of 427 nurses, respectively. The frequencies of a positive antibiotic skin test (6.9 versus 1.3%, chi-square=7.15, P=0.018), stage 1 contact urticaria syndrome (14.4 versus 7.4%, chi-square=4.33, P=0.038) and drug allergy (15.3 versus 3.6%, chi-square=18.28, P=0.000) were higher in subjects with a positive skin allergy history than in those without. Allergic rhinitis (P=0.02, OR=3.86, CI=1.23-12.06), night cough (P=0.04, OR=3.12, CI=1.03-9.41) and food allergy (P=0.00, OR=9.90, CI=3.38-29.98) were significant risk factors for drug allergy. CONCLUSIONS: Antibiotic sensitization and drug allergy occurred more frequently in nurses with a positive skin allergy history. Atopy may be an important risk factor for drug allergy.
Anti-Bacterial Agents ; Cefoperazone ; Cefotiam ; Ceftizoxime ; Cephalosporins ; Cough ; Drug Hypersensitivity ; Food Hypersensitivity ; Hand ; Hypersensitivity ; Penicillin G ; Physical Examination ; Piperacillin ; Rhinitis ; Rhinitis, Allergic, Perennial ; Risk Factors ; Skin ; Skin Tests ; Tertiary Care Centers ; Urticaria ; Surveys and Questionnaires

PURPOSE: Skin allergies through type 1 and 4 hypersensitivity reactions are the most frequent manifestations of drug allergies. We had previously experienced a case of a nurse with cefotiam-induced contact urticaria syndrome. To aid in preventing the progression of drug-induced allergic disease in nurses, we conducted a survey of tertiary hospital nurses who were likely to have been exposed professionally to antibiotics. METHODS: All 539 staff nurses at a tertiary hospital were asked to respond to a questionnaire regarding antibiotic exposure. Of the 457 nurses (84.8%) who responded, 427 (79.2%) received a physical examination of the hands and 318 (59.0%) received skin prick tests with the beta-lactam antibiotics cefotiam, cefoperazone, ceftizoxime, flomoxef, piperacillin and penicillin G. RESULTS: A positive response to at least one of the antibiotics occurred in 8 (2.6%) of the 311 subjects included in the analysis and stages 1 and 2 contact urticaria syndrome were observed in 38 (8.9%) and 3 (0.7%) of 427 nurses, respectively. The frequencies of a positive antibiotic skin test (6.9 versus 1.3%, chi-square=7.15, P=0.018), stage 1 contact urticaria syndrome (14.4 versus 7.4%, chi-square=4.33, P=0.038) and drug allergy (15.3 versus 3.6%, chi-square=18.28, P=0.000) were higher in subjects with a positive skin allergy history than in those without. Allergic rhinitis (P=0.02, OR=3.86, CI=1.23-12.06), night cough (P=0.04, OR=3.12, CI=1.03-9.41) and food allergy (P=0.00, OR=9.90, CI=3.38-29.98) were significant risk factors for drug allergy. CONCLUSIONS: Antibiotic sensitization and drug allergy occurred more frequently in nurses with a positive skin allergy history. Atopy may be an important risk factor for drug allergy.
Anti-Bacterial Agents ; Cefoperazone ; Cefotiam ; Ceftizoxime ; Cephalosporins ; Cough ; Drug Hypersensitivity ; Food Hypersensitivity ; Hand ; Hypersensitivity ; Penicillin G ; Physical Examination ; Piperacillin ; Rhinitis ; Rhinitis, Allergic, Perennial ; Risk Factors ; Skin ; Skin Tests ; Tertiary Care Centers ; Urticaria ; Surveys and Questionnaires

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