This study was performed to observe the therapeutic effects of interferon-gamma(IFN-gamma) and gamma-globulin(gamma-globulin) in experimental Pneumocystis carinii pneumonia of immune suppressed mice. After 9 weeks, trimethoprim-sulfamethoxazole(TMP-SMZ; 10-50 mg/mouse/day), mouse IFN-gamma(5 x 10(4) units/mouse/day) and mouse gamma-globulin(20 mg/mouse/day) were administered to the mice for 3 weeks by the experimental group. The therapeutic efficacy was evaluated by body weights, histopathologic and electron microscopic findings of the lungs, and number of P. carinii cysts by Gomori's methenamine silver stain. Body weights of the mice were significantly increased in the group of combination therapy of TMP-SMZ with IFN-gamma or gamma-globulin, and in the group of TMP-SMZ treatment (p < 0.05), however, little effect was found in the group of gamma-globulin alone. Histopathologic findings of P. carinii pneumonia were much improved in the group of combination therapy of TMP-SMZ with IFN-gamma. Treatment with either TMP-SMZ or IFN-gamma significantly reduced the number of cysts in the P. carinii pneumonia, but gamma-globulin alone was ineffective. In electron microscopic findings of P. carinii pneumonia, the number of trophozoites and cysts were reduced by treatment with either TMP-SMZ or IFN-gamma, and most of the cysts were empty or containing one or two intracystic bodies. The present results suggested, that combination therapy of TMP-SMZ with IFN-gamma had synergistic effects in treatment of P. carinii pneumonia in experimental mice.
Drug-Synergism ; Drug-Therapy,-Combination ; English-Abstract ; Gamma-Globulins-administration-and-dosage ; Interferon-Type-II-administration-and-dosage ; Mice- ; Trimethoprim-Sulfamethoxazole-Combination-administration-and-dosage ; *Gamma-Globulins-therapeutic-use ; *Interferon-Type-II-therapeutic-use ; *Pneumonia,-Pneumocystis-carinii-therapy ; Gamma-Globulins ; Trimethoprim-Sulfamethoxazole-Combination ; Interferon-Type-II

A 50-year-old male visited the outpatient clinic and complained of fever, poor oral intake, and weight loss. A chest X-ray demonstrated streaky and fibrotic lesions in both lungs, and chest CT revealed multifocal peribronchial patchy ground-glass opacities with septated cystic lesions in both lungs. Cell counts in the bronchoalveolar lavage fluid revealed lymphocyte-dominant leukocytosis, and further analysis of lymphocyte subsets showed a predominance of cytotoxic T cells and few T helper cells. Video-assisted wedge resection of the left upper lobe was performed, and the histologic examination was indicative of a Pneumocystis jirovecii infection. Trimethoprim-sulfamethoxazole (TMP-SMX) was orally administered for 3 weeks; however, the patient complained of cough, and the pneumonia was aggravated in the follow-up chest X-ray and chest CT. Molecular studies demonstrated mutations at codons 55 and 57 of the dihydropteroate synthase (DHPS) gene, which is associated with the resistance to TMP-SMX. Clindamycin-primaquine was subsequently administered for 3 weeks replacing the TMP-SMX. A follow-up chest X-ray showed that the pneumonia was resolving, and the cough was also alleviated. A positive result of HIV immunoassay and elevated titer of HCV RNA indicated HIV infection as an underlying condition. This case highlights the importance of careful monitoring of patients with P. jirovecii pneumonia (PCP) during the course of treatment, and the molecular study of DHPS mutations. Additionally, altering the anti-PCP drug utilized as treatment must be considered when infection with drug-resistant P. jirovecii is suspected. To the best of our knowledge, this is the first case of TMP-SMX-resistant PCP described in Korea.
Anti-Bacterial Agents/*administration & dosage ; Drug Resistance, Bacterial ; Humans ; Lung/microbiology/radiography ; Male ; Middle Aged ; Pneumocystis jirovecii/*drug effects/genetics/isolation & purification/physiology ; Pneumonia/*drug therapy/immunology/microbiology/radiography ; Sulfamethoxazole/*administration & dosage ; Trimethoprim/*administration & dosage

Chronic diarrhea with a 35 kg weight loss (75 kg to 40 kg) occurred during 2 years in an alcoholic patient was diagnosed with Isospora belli infection in the Republic of Korea. The patient, a 70-year old Korean male, had been a heavy drinker for more than 30 years. He was admitted to the Seoul National University Hospital because of long-standing diarrhea and severe weight loss. He had an increased white blood cell (WBC) count with high peripheral blood eosinophilia (36.8-39.9%) and lowered protein and albumin levels but without any evidence of immunosuppression. A parasitic infection was suspected and fecal examination was repeated 3 times with negative results. Peroral endoscopy with mural biopsy was performed in the upper jejunum. The biopsy specimens revealed villous atrophy with loss of villi together with various life cycle stages of I. belli, including trophozoites, schizonts, merozoites, macrogamonts, and microgamonts. The patient was treated successfully with oral doses of trimethoprim 160-320 mg and sulfamethoxazole 800-1,600 mg daily for 4 weeks. A follow-up evaluation at 2.5 years later revealed marked improvement of body weight (68 kg), increased protein and albumin levels, and normal WBC count with low eosinophils (3.1%). This is the first clinical case of isoporiasis with demonstration of various parasitic stages in the Republic of Korea.
Aged ; Alcoholism/*complications ; Antiparasitic Agents/administration & dosage ; Diarrhea/drug therapy/*etiology/parasitology/*pathology ; Humans ; Isospora/*isolation & purification ; Isosporiasis/*diagnosis/drug therapy/parasitology/*pathology ; Male ; Republic of Korea ; Sulfamethoxazole/administration & dosage ; Treatment Outcome ; Trimethoprim/administration & dosage

Aged ; Echinocandins ; administration & dosage ; therapeutic use ; Humans ; Leukemia, Myelomonocytic, Chronic ; pathology ; Lipopeptides ; Male ; Pneumonia, Pneumocystis ; diagnosis ; drug therapy ; pathology ; Trimethoprim, Sulfamethoxazole Drug Combination ; administration & dosage ; therapeutic use ; Uremia ; pathology

With increase of multi-drug resistant Escherichia coli in community-acquired urinary tract infections (CA-UTI), other treatment option with a therapeutic efficacy and a low antibiotic selective pressure is necessary. In this study, we evaluated in vitro susceptibility of E. coli isolates from CA-UTI to fosfomycin (FM), nitrofurantoin (NI), temocillin (TMO) as well as trimethoprim-sulfamethoxazole (SMX), ciprofloxacin (CIP) and cefepime (FEP). The minimal inhibitory concentrations were determined by E-test or agar dilution method according to the Clinical and Laboratory Standards Institute guidelines, using 346 E. coli collected in 12 Korean hospitals from March 2010 to February 2011. FM, NI and TMO showed an excellent susceptibility profile; FM 100% (346/346), TMO 96.8% (335/346), and NI 99.4% (344/346). Conversely, resistance rates of CIP and SMX were 22% (76/346) and 29.2% (101/349), respectively. FEP still retained an activity of 98.5%. In Korea, NI and TMO in addition to FM are a good therapeutic option for uncomplicated CA-UTI, especially for lower UTI.
Anti-Bacterial Agents/*administration & dosage ; Cell Survival/*drug effects ; Cephalosporins/administration & dosage ; Ciprofloxacin/administration & dosage ; Community-Acquired Infections/drug therapy/*microbiology ; Dose-Response Relationship, Drug ; Drug Combinations ; Drug Resistance, Bacterial/drug effects ; Escherichia coli/*drug effects ; Escherichia coli Infections/drug therapy/*microbiology ; Fosfomycin/administration & dosage ; Humans ; Nitrofurantoin/administration & dosage ; Penicillins/administration & dosage ; Republic of Korea ; Sulfadoxine/administration & dosage ; Treatment Outcome ; Trimethoprim/administration & dosage ; Urinary Tract Infections/diagnosis/*microbiology

With increase of multi-drug resistant Escherichia coli in community-acquired urinary tract infections (CA-UTI), other treatment option with a therapeutic efficacy and a low antibiotic selective pressure is necessary. In this study, we evaluated in vitro susceptibility of E. coli isolates from CA-UTI to fosfomycin (FM), nitrofurantoin (NI), temocillin (TMO) as well as trimethoprim-sulfamethoxazole (SMX), ciprofloxacin (CIP) and cefepime (FEP). The minimal inhibitory concentrations were determined by E-test or agar dilution method according to the Clinical and Laboratory Standards Institute guidelines, using 346 E. coli collected in 12 Korean hospitals from March 2010 to February 2011. FM, NI and TMO showed an excellent susceptibility profile; FM 100% (346/346), TMO 96.8% (335/346), and NI 99.4% (344/346). Conversely, resistance rates of CIP and SMX were 22% (76/346) and 29.2% (101/349), respectively. FEP still retained an activity of 98.5%. In Korea, NI and TMO in addition to FM are a good therapeutic option for uncomplicated CA-UTI, especially for lower UTI.
Anti-Bacterial Agents/*administration & dosage ; Cell Survival/*drug effects ; Cephalosporins/administration & dosage ; Ciprofloxacin/administration & dosage ; Community-Acquired Infections/drug therapy/*microbiology ; Dose-Response Relationship, Drug ; Drug Combinations ; Drug Resistance, Bacterial/drug effects ; Escherichia coli/*drug effects ; Escherichia coli Infections/drug therapy/*microbiology ; Fosfomycin/administration & dosage ; Humans ; Nitrofurantoin/administration & dosage ; Penicillins/administration & dosage ; Republic of Korea ; Sulfadoxine/administration & dosage ; Treatment Outcome ; Trimethoprim/administration & dosage ; Urinary Tract Infections/diagnosis/*microbiology

BACKGROUND: Acute pyelonephritis in women can be treated with trimethoprim-sulfamethoxazole (SXT), fluoroquinolone, aminoglycosides, second- and third- generation cephalosporins. The purpose of this study is to provide basic informations for the choice of the most effectve and economic first-line antibiotics among several agents to clinicians, who manage community- acquired acute pyelonephritis. METHODS: We investigated antibiotic sensitivities of 130 organisms isolated from urine culture of 165 patients, who admitted to Catholic University St. Vincent's Hospital due to community-acquired acute pyelonephritis from February 2001 to November 2002. All those patients had more than 105 cfu/mL on urine culture and we analyzed the usage of antibiotics and clinical course in those patients. RESULTS: Among 130 isolates, 120 isolates were E. coli, 6 K. pneumoniae, 1 K. oxytoca, 1 Enterobacter aerogenes and 2 Proteus mirabilis. Among 120 E. coli, the rates of resistance were 59.2% to piperacillin, 58.3% to cephalothin, 36.7% to sulfamethoxazole, 19.2 % to gentamicin, and 7.5% to ciprofloxacin in order. For 120 E. coli isolates, 100%, 99.2%, 99.2%, 99.2%, and 97.5% were susceptible to imipenem, cefotaxime, cefuroxime, amikacin, and piperacillin/tazobactam, respectively. Among 165 patients, 130 patients who had positive urine or blood culture, were divided into three groups according to the first-line antibiotics administered on the day of admission. Gentamicin (5 mg/kg q 24h) were infused to 90 patients, and 9 (10%) of 90 patients revealed clinical manifestations of therapeutic failure such as persistent fever and pyuria in group I. Cefuroxime were administered to 36 patients in group II and all 36 patients revealed evidences of clinical success such as defervescence and absence of pyuria. Intravenous antibiotics changed to oral administration of the first-, second-cephalosporin, and trimethoprim- sulfamethoxazole in all patients except one patient, who received oral fluoroquinolone according to the results of antibiotic sensitivities. CONCLUSION: Cefuroxime, amikacin, and the third- generation cephalosporins showed excellent antibacterial activity against isolated organisms from women with acute pyelonephritis in this study, and gentamicin could be used as initial empiric regimen with careful monitoring of clinical response and antibiotic sensitivities of isolated microorganisms. These findings would be useful informations to physicians, who are trying to use low-priced antibiotics with narrow spectrum antibacterial activity, sparing more expensive and broad spectrum antibiotics in managing urinary tract infections.
Administration, Oral ; Amikacin ; Aminoglycosides ; Anti-Bacterial Agents* ; Cefotaxime ; Cefuroxime ; Cephalosporins ; Cephalothin ; Ciprofloxacin ; Enterobacter aerogenes ; Female ; Fever ; Gentamicins ; Humans ; Imipenem ; Piperacillin ; Pneumonia ; Proteus mirabilis ; Pyelonephritis* ; Pyuria ; Sulfamethoxazole ; Trimethoprim, Sulfamethoxazole Drug Combination ; Urinary Tract Infections

The paper is to report the pharmacokinetics of sulfamethoxazole in healthy Han volunteers living at plain (PH) and native Han and Tibetan healthy volunteers living at high altitude (HNH and HNT). After healthy volunteers were administrated orally cotrimoxazole tablets, plasma concentration of sulfamethoxazole and metabolite N4-acetylsulfamethoxazole was determined by RP-HPLC, and plasma concentration-time data were analyzed by DAS 2.0 software to get the related pharmacokinetic parameters. The main pharmacokinetic parameters t(1/2) of sulfamethoxazole in PH, HNH and HNT were, respectively, 9.30 +/- 1.11, 10.99 +/- 1.23 and 10.44 +/- 1.05 h; tmax were 1.4 +/- 0.3, 2.0 +/- 1.1 and 1.8 +/- 0.4 h; Cmax were 94.42 +/- 15.26, 89.33 +/- 7.67 and 87.43 +/- 11.61 micro x mL(-1); AUC(0-t) were 1202.5 +/- 238.3, 1 434.7 +/- 193.9 and 1302.8 +/- 103.0 microg x h x mL(-1); AUC(0-infinity) were 1240.7 +/- 255.3, 1511.5 +/- 211.9 and 1363.9 +/- 116.5 microg x h x mL(-1); CL were 1.01 +/- 0.22, 0.81 +/- 0.12 and 0.89 +/- 0.08 L x h(-1) x kg(-1); V were 13.27 +/- 1.73, 12.81 +/- 2.15 and 13.28 +/- 1.20 L x kg(-1). Sulfamethoxazole pharmacokinetic parameters of HNH and HNT were significantly different from that of PH. The t(1/2) was significantly higher and the CL was significantly lower in HNH and HNT than that in PH, and the AUC(0-infinity) was significantly lower in HNT compared with HNH. This study found significant changes in the disposition of sulfamethoxazole under the special environment of high altitude hypoxia. This finding may provide some references for clinical rational application of sulfamethoxazole in HNH and HNT.
Adult ; Altitude ; Anti-Infective Agents ; administration & dosage ; pharmacokinetics ; Area Under Curve ; Asian Continental Ancestry Group ; ethnology ; China ; ethnology ; Chromatography, High Pressure Liquid ; Erythrocytes ; metabolism ; Humans ; Hypoxia ; metabolism ; Male ; Protein Binding ; Sulfamethoxazole ; analogs & derivatives ; blood ; pharmacokinetics ; Tablets ; Trimethoprim, Sulfamethoxazole Drug Combination ; administration & dosage ; pharmacokinetics ; Young Adult