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Background: Lopinavir/ritonavir (LPV/r) could be associated with adverse cardiac event. Antiretroviral drugs containing LPV/r are used concurrently with sulfamethoxazole/trimethoprim (SMX/TMP) which may also be associated with adverse cardiac events in the management of human immunodeficiency virus and co-infection. The concurrent use of these drugs may precipitate synergistic adverse cardiac events. This work, therefore, evaluates the possible toxicological interaction of co administered LPV/r and SMX/TMP on cardiac function and architecture of albino rats. Methods: Seventy five (75) animals which were divided into five groups (A-E) of fifteen (15) animals each were used in this study. Animals in Group A, which served as the control, were treated with 1% ethanol orally. Animals in Group (B-E) were treated with oral doses of SMX/TMP (11.2/2.3 mg/kg), LPV/r (11.4/2.9 mg/kg), and combine doses of SMX/TMP+LPV/r for 2-8 weeks, respectively. Blood sample was collected and evaluated for pack cell volume, hemoglobin, red blood cell and white blood cell. Cardiac tissues were evaluated for malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSHPX), and histopathological changes. Results: Treatment with SMX/TMP LPV/r and their combine doses produced no significant effect on cardiac weight. SMX/TMP significantly decreased red blood cell and hemoglobin while LPV/r produced no significant hematologic effect. Combine doses of these agents produced no synergistic hematologic effects. Treatment with a single and combine doses of these agents produced time-dependent decrease in SOD, GSHPX and increase in MDA, but no synergistic effects were produced by their combine doses. Normal cardiac myocytes with patchy collection of mononuclear inflammatory cells infiltration of the interstitium were observed after treatment with single and combined doses of these agents but without any synergistic effect when agents were co-administered. Conclusion: In this study, the co-administration of SMX/TMP and LPV/r did not produce any significant synergistic effects on all the evaluated parameters; hence, the concurrent use of these agents in the management of HIV and co-infections may be safe on cardiac function and structure.
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Background: Human immunodeficiency virus/acquired immune deficiency syndrome is usually associated with co-infections which has allow the concurrent use of sulfamethoxazole/trimethoprim (SMX/TMP)+Lopinavir/ritonavir (LPV/r). The concurrent use of these drugs may have possible adverse effects on the kidney because they are individually associated with adverse renal events. This study, therefore evaluates the possible effect of co-administered SMX/TMP+LPV/r on kidney function and architecture of albino rats. Methods: Seventy five (75) animals which were divided into five groups were used in this study. Group A, which served as control, contained 15 animals which were treated with 1% ethanol orally. Group B-E, which contained 15 animals each, was further subdivided into three groups of five animals each. Animals in these groups were treated with oral doses of SMX/TMP (11.2/2.3 mg/kg), LPV/r (11.4/2.9 mg/kg), and combined doses of SMX/TMP+LPV/r for 2-8 weeks respectively. Serum levels of creatinine, urea, and uric acid were evaluated. Kidney tissue was evaluated for malondialdehyde (MDA), superoxide dismutase (SOD), and histopathological changes. Results: Treatment with single doses of SMX/TMP, and LPV/r, produced a time-dependent increase in serum creatinine and urea. But no significant synergistic effects on serum creatinine and urea were observed when these agents were co-administered. Treatment with single and combine doses of these agents had no significant effects on serum uric acid level. Treatment with single agents produced time-dependent increase in kidney MDA and decrease in SOD level but without any significant effects when these agents were co-administered. Kidney of animals treated with single doses of these agents showed hypercellarity of the interstitium of the glomeruli and vascular congestion with no synergistic effects when these agents were co-administered. Conclusion: Concurrent use of SMX/TMP+LPV/r in the management of HIV and co-infection may not have any deleterious effect on the renal system.
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INTRODUCTION: Amphotericin B, azole or sulfamide drugs are used for treatment of patients with paracoccidioidomycosis. Among the azole drugs, voriconazole was active in vitro against Paracoccidioides brasiliensis and showed efficacy in the treatment of patients infected with this fungus.In the present study the antifungal activity of voriconazole and of other drugs was compared in a rat model of paracoccidioidomycosis. METHODS: Wistar rats were inoculated intravenously with the BOAS strain of P. brasiliensis and antifungal drugs were administered to the animals by gavage at the following doses (mg/kg weight/day): voriconazole (5 to 20), ketoconazole (12 to 15), fluconazole (6), itraconazole (4), and sulfamethoxazole-trimethoprim (120 to 150). The antifungal activity of the drugs was assessed by determining the P. brasiliensis colony forming units in the lungs and spleen of the animals at the end of treatment and by a survival study. RESULTS: Voriconazole reduced the total tissue fungal burden of P. brasiliensis, particularly at doses of ≥10mg/kg weight/day but its antifungal activity was less intense than that of fluconazole, itraconazole and sulfamethoxazole-trimethoprim. The mean survival of animals treated with the last three drugs, 29.1±10.7, 26.1± 10.1 and 28.4±9.6 days, respectively, was higher than that achieved with voriconazole 10mg/kg weight/day (18.5±8.3 days) and that observed in untreated animals (15.7±3.6 days). CONCLUSIONS: At doses similar to those used for clinical treatment, voriconazole showed lower antifungal activity in experimental rat paracoccidioidomycosis than that obtained with itraconazole and sulfamethoxazole-trimethoprim.
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Animals , Female , Rats , Antifungal Agents/pharmacology , Paracoccidioidomycosis/drug therapy , Disease Models, Animal , Pyrimidines/pharmacology , Rats, Wistar , Triazoles/pharmacologyABSTRACT
Objective To evaluate the prophylactic efficacy of compound sulfamethoxazole (SMZco)combined with ganciclovir on severe pulmonary infection in the early stage of renal transplantation. Methods Between January 2005 and January 2006,two hundred and forty renal allograft patients in our hospital were enrolled in this study.All the patients were divided into two groups.Group A(n=84)received oral SMZco combined with intravenous ganciclovir.Group B(n=156)received intravenous ganciclovir only as control.According to the time of SMZco administration,group A was divided into two subgroups:group A1(within 2weeks after transplantation,n=43)and group A2(more than 2 weeks after transplantation,n=41).All the patients were followed up for 9 months.Incidence of pulmonary infection and effects on graft function by SMZco at different time point were investigated. Results The incidence of severe pulmonary infection and mortality of infection were significantly lower in group A than those in group B (2/84 vs 16/156,P=0.027;0/2 vs 2/16,P＜0.01).There were no significant differences between two groups in terms of age,gender,warm or cold ischemia,complement dependent cytotoxieity test results,incidence of urinary infection and Scr.The incidence of elevatedScr was significantly lower in group A2 than that in group A1(15/43 vs 2/41,P＜0.01),however,all the elevated Scr returned to basal level within 1 week after SMZco was discontinued.Conclusions Oral SMZco combined with ganciclovir administration after renal transplantation is effective on preventing severe pulmonary infection and thus improves graft and recipient survival.The administration of oral SMZco initiated more than 2 weeks after transplantation is better for graft function.
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OBJECTIVE To investigate the antimicrobial-resistant profile of sulfamethoxazole-trimethoprim(SXT) resistant Staphylococcus aureus.METHODS The strains of S.aureus(SAU) were isolated from clinical specimens by routine methods.The identification and susceptibility test of the isolates were determined by Automated Microbiology Analyzer.Disk-diffusion was used for detecting meticillin-resistant S.aureus(MRSA).?2 Test was made to identify the significance of difference.RESULTS 68.0% Of isolates were referred as MRSA.The resistant rates of the isolates of SAU to SXT was 30.8%.The resistant rate of the isolates of MRSA and MSSA to SXT were 27.4% and 38%.60.5% And 71.3% of isolates were referred as MRSA from the SXT-resistant group and MRSA from the SXT-sensitive group.The resistant rate of MRSA from the group of SXT-resistant to tetracycline,levofloxacin and rifampicin were all significantly lower than those of isolates from the SXT-sensitive group(all P
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Antimicrobial agents played a miraculous role in the treatment of bacterial infections until resistant bacteria became widespread. Besides antimicrobial-resistant bacteria, many factors can influence the cure of infection. Nocardia infection may be a good example which is difficult to cure with antimicrobial agents alone. A 66-year-old man developed soft tissue infection of the right buttock and thigh. He was given prednisolone and azathioprine for pachymeningitis 3 months prior to admission. Despite surgical and antimicrobial treatment (sulfamethoxazole-trimethoprim), the infection spread to the femur and osteomyelitis developed. The case showed that treatment of bacterial infection is not always as successful as was once thought because recent isolates of bacteria are more often resistant to various antimicrobial agents, intracellular parasites are difficult to eliminate even with the active drug in vitro, and infections in some sites such as bone are refractory to treatment especially when the patient is in a compromised state. In conclusion, for the treatment of infections, clinicians need to rely on laboratory tests more than before and have to consider the influence of various host factors.