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

BACKGROUND: Combicin(R) is a new product of beta- lactam and beta-lactamase inhibitor combination which has antibacterial activity against aerobic and anaerobic bacteria, comprised of piperacillin and sulbactam. A phase III randomized clinical trial of Combicin(R) was done to evaluate and compare the efficacy and safety of piperacillin/sulbactam (Combicin(R)) with piperacillin in the treatment of urinary tract infection. METHODS: A total of 128 adult patients with acute urinary tract infection were enrolled and randomized into one of the two treatment groups during the period from August 1997 to September 1999 in Severance Hospital and Asan Medical Center, Seoul, Korea. Sixty-five patients were excluded in the analysis according to the exclusion criteria, and the rest 63 patients (3 men, 60 women) were eligible for the study. Clinical and bacteriologic responses were evaluated at entry and during the study period. Adverse effects were monitored by daily examination of the patients and periodic evaluations of laboratory findings. Statistical analyses were done by Chi-square test, Fisher's exact test, and Student t-test. RESULTS: Symptoms and signs such as fever, pyuria, dysuria, frequency, tenesmus, and costovertebral angle tenderness showed improvement in both group. Most commonly isolated microorganism was E. coli. The bacteriological eradication was found in 96.7% of the Combicin(R)-treated patients and in 90.9% of the piperacillin-treated patients. Adverse drug reactions in Combicin(R)-treated patients and piperacillin-treated patients occurred in 3.33% (2/60) and 5.88% (4/68) of the patients, respectively. Adverse events included liver function test elevation, drug fever, rash, indigestion, leukopenia, and nausea. Combicin(R) was well tolerated and side effects were negligible. CONCLUSION: Combicin(R) is safe and effective in the treatment of urinary tract infections.
Adult ; Bacteria, Anaerobic ; beta-Lactamases ; Chungcheongnam-do ; Drug-Related Side Effects and Adverse Reactions ; Dyspepsia ; Dysuria ; Exanthema ; Fever ; Humans ; Korea ; Leukopenia ; Liver Function Tests ; Male ; Nausea ; Piperacillin ; Pyuria ; Seoul ; Sulbactam ; Urinary Tract Infections* ; Urinary Tract*

Acinetobacter Infections ; drug therapy ; Acinetobacter baumannii ; drug effects ; pathogenicity ; Adult ; Anti-Bacterial Agents ; administration & dosage ; therapeutic use ; Burns ; drug therapy ; microbiology ; Cefoperazone ; administration & dosage ; therapeutic use ; Humans ; Middle Aged ; Minocycline ; administration & dosage ; therapeutic use ; Retrospective Studies ; Sulbactam ; administration & dosage ; therapeutic use ; Thienamycins ; adverse effects ; therapeutic use ; Young Adult