Anti-proliferative effects of the combination of Sulfamethoxazole and Quercetin via caspase3 and NFkB gene regulation: an in vitro and in vivo study.

Combination therapy comprising natural polyphenols and anticancer drugs has been used to decrease the adverse effects and increase the effectiveness and antioxidant activities of the drugs. The antioxidant and anticancer effects of quercetin (Q), a nutritive polyphenol, have been observed both in vitro and in vivo. Likewise, the anticancer activity of sulfamethoxazole (S) has been demonstrated in vitro and in vivo. This study aimed to investigate the in vitro and in vivo anticancer effects of Q alone and in combination with S. The in vitro effects of S, Q, and S + Q on HCT-116, HepG2, MCF-7, and PC3 cell lines were examined. Additionally, the in vivo effects of these drugs were evaluated using Ehrlich ascites carcinoma (EAC) tumor-bearing mice. The in vitro data revealed the potent anticancer activity of S + Q through the induction of apoptosis and cell cycle arrest. The EAC-inoculated mice treated with S + Q presented with elevated SOD, GSH, CAT, and TAC levels and decreased malondialdehyde levels compared with the untreated EAC group, thus revealing the antioxidant and protective actions of S + Q against EAC cell invasion. Furthermore, the downregulation of NFkB and upregulation of the caspase3 gene in the EAC-inoculated mice treated with the S + Q indicated the induction of the apoptotic pathway and decrease in both cell proliferation and metastasis. In conclusion, the combination of S and Q might exert anticancer effects by inducing apoptosis and exhibiting selective toxicity against the cancer cells and thereby protecting the vital organs.

Clinical Effect of Doxycycline Combined with Compound Sulfamethoxazole and Rifampicin in the Treatment of Brucellosis Spondylitis.

OBJECTIVE: The purpose of this study was to determine the clinical value of triple antibiotic therapy consisting of doxycycline, compound sulfamethoxazole and rifampicin in the treatment of brucellosis spondylitis. METHODS: A retrospective analysis was performed on 100 patients with brucellosis spondylitis admitted to the First Affiliated Hospital of Hebei North University from March 2016 to June 2019. Patients were divided into the following two groups: the control group (n = 50) treated with dual antibiotic therapy (rifampicin + compound sulfamethoxazole), and the observation group (n = 50) treated with triple antibiotic therapy (rifampicin + doxycycline + compound sulfamethoxazole). The treatment effect, low back pain relief, levels of erythrocyte sedimentation rate (ESR), procalcitonin (PCT) and C-reactive protein (CRP), as well as the adverse reactions were compared between the two groups. RESULTS: The response rate of the observation group was significantly higher than that of the control group (P < 0.05). Before treatment, there was no significant difference in the low back pain assessed by the visual analogue scale (VAS), or levels of ESR, PCT and CRP between the two groups (P > 0.05). But after treatment, the VAS score and the levels of ESR, PCT and CRP in observation group were lower than those in the control group (P < 0.05). No significant difference was found in the incidence of adverse reactions (P > 0.05). CONCLUSION: The triple antibiotic therapy of doxycycline, compound sulfamethoxazole and rifampicin is effective in the treatment of brucellosis spondylitis. It can significantly alleviate patients' back pain and inflammation with a high safety profile, which is worthy of clinical application.

Paracoccidioidomycosis due to Paracoccidioides brasiliensis S1 associated with acquired immunodeficiency syndrome: A case report / Paracoccidioidomicosis por Paracoccidioides brasiliensis S1 asociado al síndrome de inmunodeficiencia adquirida: A propósito de un caso

BACKGROUND: Paracoccidioidomycosis (PCM) is an endemic disease in Latin America. In immunocompetent hosts, PCM occurs in two main clinical forms: acute and chronic. However, in HIV-infected patients PCM may show up simultaneous manifestations of acute and chronic forms. CASE REPORT: We present the case of a patient diagnosed with HIV who had disseminated skin lesions and generalized lymphadenopathy, as well as respiratory and central nervous system involvement. The PCM diagnosis was confirmed by direct KOH examination, double immunodiffusion and the isolation of the fungus in samples of an abscess in the subcostal region. The isolate was identified as Paracoccidioides brasiliensis S1 by species-specific PCR using primers for protein-coding gene GP43 (exon 2) followed by PCR-RFLP of the alpha-tubulin gene. CONCLUSIONS: There are few data in literature reporting species-specific molecular identification of Paracoccidioides in HIV/PCM patients. Therefore, this case report may contribute to improve the knowledge about this severe disease, its causative cryptic species, and its consequences to patients

ANTECEDENTES: La paracoccidioidomicosis (PCM) es una enfermedad endémica en Latinoamérica. En los pacientes inmunocompetentes, la PCM cursa con dos principales formas: aguda y crónica. Sin embargo, los pacientes infectados por el VIH pueden presentar manifestaciones simultáneas de las dos formas clínicas. CASO CLÍNICO: Se presenta el caso de un paciente VIH-positivo, con lesiones cutáneas diseminadas, linfadenopatía generalizada y afectación del sistema nervioso central y respiratorio. El diagnóstico de PCM se confirmó mediante un examen directo con KOH, doble inmunodifusión y el aislamiento del hongo en cultivo, a partir de muestras de un absceso en la región subcostal. La cepa aislada se identificó como Paracoccidioides brasiliensis S1 mediante PCR especie-específica del gen codificador de la proteína GP43 (exón 2), seguida de PCR-RFLP del gen de la alfa-tubulina. CONCLUSIONES: Existen pocos datos en la literatura que describan la identificación molecular especie-específica de Paracoccidioides en pacientes con VIH/PCM. Por lo tanto, la presentación de este caso clínico puede contribuir a mejorar el conocimiento sobre esta enfermedad grave, la especie críptica implicada y sus consecuencias para los pacientes

Tongue lesion due to Cryptococcus neoformans as the first finding in an HIV-positive patient / Lesión lingual por Cryptococcus neoformans como primer hallazgo clínico en una paciente VIH positiva

BACKGROUND: Cryptococcosis is a severe universally distributed mycosis which mainly affects immunocompromised hosts. This mycosis is caused by yeasts of two species complex of the genus Cryptococcus: Cryptococcus neoformans and Cryptococcus gattii. Meningeal cryptococcosis is the most frequent clinical presentation of this disseminated mycosis. The oral mucosa involvement is extremely unusual. CASE REPORT: We present a case of cryptococcosis with an unusual clinical form. The patient was assisted because she had an ulcerated lesion on the lingual mucosa. Encapsulated yeasts compatible with Cryptococcus were found in microscopic exams of wet preparations from lingual ulcer clinical samples obtained for cytodiagnosis and mycological studies. Cryptococcus neoformans (C. neoformans var. grubii VNI) was isolated in culture. This patient did not know her condition of HIV seropositive before the appearance of the tongue lesion. CONCLUSIONS: The involvement of the oral mucosa is uncommon in this fungal infection, but is important to include it in the differential diagnosis in HIV positive patients

ANTECEDENTES: La criptococosis es una micosis grave de distribución universal que afecta principalmente a los huéspedes inmunodeficientes. Se han definido dos complejos de especies patógenas: Cryptococcus neoformans y Cryptococcus gattii. La meningoencefalitis es la presentación clínica más frecuente de esta micosis sistémica. La afectación de la mucosa oral es extremadamente rara. CASO CLÍNICO: Presentamos el caso de una paciente VIH positiva con una forma clínica inusual de criptococosis. La enferma presentaba una lesión ulcerada en la punta de la lengua. El examen microscópico en fresco de la escarificación y de la biopsia de esta lesión mostraron levaduras capsuladas compatibles con Cryptococcus. Se obtuvo Cryptococcus neoformans (C. neoformans var. grubii VNI) en los cultivos. La paciente conoció su estado inmunológico (infección por VIH) en el contexto de esta enfermedad oportunista. CONCLUSIONES: La afectación de la mucosa oral es poco común en esta infección fúngica, pero es importante incluirla en el diagnóstico diferencial en pacientes VIH positivos

Nocardia kroppenstedtii: a rare pathogen isolated from the spinal vertebral abscess of a patient on long-term immunosuppressive therapy.

OBJECTIVE: Nocardia kroppenstedtii was isolated from the spinal vertebral abscess of a 78-year-old patient presenting with mid-thoracic pain and bilateral lower limb weakness and numbness. The patient was on long-term immunosuppressive therapy with steroids for underlying autoimmune hemolytic anemia. Investigations showed a T5 pathological fracture and vertebra plana with the erosion of the superior and inferior endplates. There was evidence of paraspinal collection from the T4-T6 vertebrae with an extension into the spinal canal. Analysis of Nocardia 16S rRNA (99.9%, 1395/1396 nt) and secA1 gene (99.5%, 429/431 nt) fragments showed the highest sequence similarity with Nocardia kroppenstedtii type strain (DQ157924), and next with Nocardia farcinica (Z36936). The patient was treated with intravenous carbapenem and oral trimethoprim-sulfamethoxazole for four weeks, followed by another six months of oral trimethoprim-sulfamethoxazole. Despite the improvement of neurological deficits, the patient required assistive devices to ambulate at discharge. This study reports the first isolation of N. kroppenstedtii from the spinal vertebral abscess of a patient from Asia. Infections caused by N. kroppenstedtii may be underdiagnosed as the bacterium can be misidentified as N. farcinica in the absence of molecular tests in the clinical laboratory.

Sulfamethoxazole drug stress upregulates antioxidant immunomodulatory metabolites in Escherichia coli.

Escherichia coli is an important model organism in microbiology and a prominent member of the human microbiota1. Environmental isolates readily colonize the gastrointestinal tract of humans and other animals, and they can serve diverse probiotic, commensal and pathogenic roles in the host2-4. Although certain strains have been associated with the severity of inflammatory bowel disease (IBD)2,5, the diverse immunomodulatory phenotypes remain largely unknown at the molecular level. Here, we decode a previously unknown E. coli metabolic pathway that produces a family of hybrid pterin-phenylpyruvate conjugates, which we named the colipterins. The metabolites are upregulated by subinhibitory levels of the antifolate sulfamethoxazole, which is used to treat infections including in patients with IBD6,7. The genes folX/M and aspC/tyrB involved in monapterin biosynthesis8-10 and aromatic amino acid transamination,11 respectively, were required to initiate the colipterin pathway. We show that the colipterins are antioxidants, harbour diverse immunological activities in primary human tissues, activate anti-inflammatory interleukin-10 and improve colitis symptoms in a colitis mouse model. Our study defines an antifolate stress response in E. coli and links its associated metabolites to a major immunological marker of IBD.

Síndrome de secreción inadecuada de hormona antidiurética en paciente con linfoma difuso de células grandes B / Syndrome of inappropriate antidiuretic hormone secretion in a patient with diffuse large B-cell lymphoma

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Pharmacokinetics of Sulfamethoxazole and Trimethoprim During Venovenous Extracorporeal Membrane Oxygenation: A Case Report.

Extracorporeal membrane oxygenation (ECMO) therapy could affect drug concentrations via adsorption onto the oxygenator and/or associated circuit. We describe a case of a 33-year-old man with severe respiratory failure due to Pneumocystis jirovecii infection on a background of recently diagnosed human immunodeficiency virus infection. He required venovenous ECMO therapy for refractory respiratory failure. Intravenous sulfamethoxazole-trimethoprim (100 and 20 mg/kg/day) was administered in a dosing regimen every 6 hours. Pre-oxygenator, post-oxygenator, and arterial blood samples were collected after antibiotic administration and were analyzed for total sulfamethoxazole and trimethoprim concentrations. The peak sulfamethoxazole and trimethoprim concentrations were 122 mg/L and 5.3 mg/L, respectively. The volume of distribution for sulfamethoxazole was 0.37 and 2.30 L/kg for trimethoprim. The clearance for sulfamethoxazole was 0.35 ml/minute/kg and for trimethoprim was 1.64 ml/minute/kg. The pharmacokinetics of sulfamethoxazole and trimethoprim appear not to be affected by ECMO therapy, and dosing adjustment may not be required.

Imaging Findings of Pulmonary Nocardiosis Mimicking Bronchiectasis.

Nocardia species usually cause opportunistic infections, and the frequency of these infections is increasing owing to the growing population of immunocompromised hosts. However, Nocardia may sometimes causes an infectious disease in immunocompetent hosts. Herein, we report two cases of pulmonary nocardiasis in immunocompetent individuals, whose chest computed tomography (CT) findings mimicked bronchiectasis. Samples of bronchalveolar lavage (BAL) fluid obtained by bronchoscopy showed filamentous, branching, gram-positive rods, acid-fast filamentous branching rods, and a colony of suspected Nocardia was cultured. Based on 16sRNA and hsp65 gene sequence analysis, case 1 was identified as N. cyriacigeorgica, but case 2 was not matched. The patients responded well to treatment with the combination of sulfamethoxazole and linezolid.

Criptococosis cutánea / Cutaneous cryptococcosis

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Toxicity of sulfamethazine and sulfamethoxazole and their removal by a green microalga, Scenedesmus obliquus.

A comprehensive ecotoxicological evaluation of a sulfamethazine (SMZ) and sulfamethoxazole (SMX) mixture was conducted using an indicator microalga, Scenedesmus obliquus. The toxicological effects of this mixture were studied using microalgal growth patterns, biochemical characteristics (total chlorophyll, carotenoid, carbohydrate, fatty acid methyl ester), and elemental and Fourier-transform infrared spectroscopy analyses. The 96-h half maximal effective concentration (EC50) of the SMZ and SMX mixture was calculated to be 0.15 mg L-1 according to the dose-response curves obtained. The chlorophyll content decreased with elevated SMZ and SMX concentrations, while the carotenoid content initially increased and then decreased as concentration raised. The unsaturated fatty acid methyl esters (FAMEs) content was enhanced with higher SMZ and SMX concentrations, while that of saturated FAMEs simultaneously decreased due to SMZ and SMX stress. Elemental analyses showed an improved percentage of nitrogen and sulfur in the microalgal biomass as SMZ and SMX concentrations increased. The microalga S. obliquus was shown to biodegrade the chemicals tested and removed 31.4-62.3% of the 0.025-0.25 mg SMZ L-1 and 27.7-46.8% of the 0.025-0.25 mg SMX L-1 in the mixture after 12 days of cultivation. The greater biodegradation observed at higher SMZ and SMX concentrations indicates that microalgal degradation of SMZ and SMX could act as an efficient adaptive mechanism to antibiotics.

A co-infection of varicella-zoster virus and Pneumocystis jirovecii in a non-HIV immunocompromised patient: a case report.

BACKGROUND: Varicella-zoster virus (VZV) causes herpes zoster. Pneumocystis jirovecii (PJ) also causes pneumonia in immunocompromised hosts. Although both cause opportunistic infections, it is rare to have a co-infection in a non-human immunodeficiency virus carrier. CASE PRESENTATION: An 84-year-old woman with hemolytic anemia referred because of acute respiratory failure. She had received prednisolone without PJ pneumonia prevention. She developed dyspnea and desaturation while eating, and thus was treated based on a presumptive diagnosis of aspiration pneumonia. Physical examination revealed a vesicular rash on the left side of her neck suggesting herpes zoster infection. Polymerase chain reaction of her sputum for PJ and VZV was positive, which confirmed a diagnosis of pneumonia due to PJ and VZV co-infection. Despite acyclovir and sulfamethoxazole and trimethoprim administration, she died on hospital day 19. CONCLUSIONS: Clinicians should suspect PJP when patients on systemic corticosteroids develop pneumonia and they have not received prophylactic treatment for PJP in non-HIV carriers. When such patients have a VZV rash, clinicians should aggressively seek signs of opportunistic infections. Our case hereby highlights the importance of recognizing the possibility of a VZV and PJ co-infection.

Myroides odoratimimus urinary tract infection in an immunocompromised patient: an emerging multidrug-resistant micro-organism.

Background: Myroides spp. are common environmental organisms and they can be isolated predominantly in water, soil, food and in sewage treatment plants. In the last two decades, an increasing number of infections such as urinary tract infections and skin and soft tissue infections, caused by these microorganisms has been reported. Selection of appropriate antibiotic therapy to treat the infections caused by Myroides spp. is difficult due to the production of a biofilm and the organism's intrinsic resistance to many antibiotic classes. Case presentation: We report the case of a 69-year-old immunocompromised patient who presented with repeated episodes of macroscopic haematuria, from Northern Italy.A midstream urine sample cultured a Gram negative rod in significant amounts (> 105 colony-forming units (cfu)/mL), which was identified as Myroides odoratimimus. The patient was successfully treated with trimethoprim/sulfamethoxazole after antibiotic susceptibility testing confirmed its activity. Conclusion: This case underlines the emergence of multidrug resistant Myroides spp. which are ubiquitous in the environment and it demands that clinicians should be more mindful about the role played by atypical pathogens, which may harbour or express multidrug resistant characteristics, in immunocompromised patients or where there is a failure of empiric antimicrobial therapy.

Trends and patterns of national antimicrobial consumption in Japan from 2004 to 2016.

Frequent use of broad-spectrum antimicrobial classes has been reported in Japan; however, little is known about the long-term trend of national antimicrobial consumption, and that of individual agents. This study analyzed the national sales data of systemic antimicrobials from 2004 to 2016, derived from the IMS Japan Pharmaceutical Market database, to assess the consumption patterns of antimicrobial classes and agents in Japan. The number of defined daily doses per 1000 inhabitants per day (DID) was calculated for each antimicrobial agent. During the last 13 years, total antimicrobial consumption fluctuated by only 5% around the average of 14.41 DID. In 2016, the most used class was macrolides (32%), followed by cephalosporins (28%) and fluoroquinolones (19%). Oral agents comprised a large proportion (93%) of antimicrobial consumption. The most used agent, clarithromycin, accounted for 25% of all oral compounds used in 2016. The consumption of oral agents with high bioavailability, such as fluoroquinolones, amoxicillin, and sulfamethoxazole/trimethoprim increased, whereas that of cephalosporins decreased. In 2016, ceftriaxone was the most consumed parenteral agent, followed by cefazolin. The consumption of parenteral agents increased after 2009 when high-dose regimens of piperacillin/tazobactam, meropenem, and ampicillin/sulbactam were approved by the health insurance system. National antimicrobial consumption has been stable over the last 13 years. Moreover, shifts in the use of agents with high bioavailability and those approved for high-dose regimens were observed. However, the increased use of broad-spectrum agents is worrisome. A multifaceted approach is required to reduce overall antimicrobial consumption.

Clinical outcomes in patients hospitalized with cellulitis treated with oral clindamycin and trimethoprim/sulfamethoxazole: The role of weight-based dosing.

OBJECTIVES: Trimethoprim/sulfamethoxazole (TMP/SMX) and clindamycin are frequently prescribed to treat cellulitis. The primary objective was to determine if weight-based dosing of these antibiotics is associated with better outcomes in cellulitis. The secondary objective was to assess variables associated with clinical failure among hospitalized patients with cellulitis with or without cutaneous abscess. METHODS: This multi-center retrospective cohort study was conducted from January 1, 2010 to September 4, 2014. Adult patients admitted for cellulitis who received a minimum of seven days of therapy and discharged on oral clindamycin or TMP/SMX were included. Binary univariate and multivariate logistic regression analyses were performed to identify risk factors for clinical failure, including the impact of dose adequacy of clindamycin and TMP/SMX on clinical outcomes. RESULTS: A total of 208 cases met inclusion criteria. Of these cases, 120 (57.7%) received inadequate dosing of clindamycin (<10 mg/kg/day) or TMP/SMX (<5 mg TMP/kg per day) while 88 (42.3%) received adequate dosing. Clinical failure occurred in 36/120 (30%) and 15/88 (17%) of patients receiving inadequate and adequate doses, respectively (p = 0.032). Upon univariate analysis length of stay ≥ 7 days (OR = 2.96, p = 0.046) and inadequate dosing (OR = 2.09, p = 0.034) were associated with clinical failure. Upon multivariate analysis, inadequate dosing was independently associated with clinical failure (OR = 2.01, p = 0.032). CONCLUSION: Inadequate dosing of clindamycin and TMP/SMX is independently associated with clinical failure in patients hospitalized with cellulitis. Further prospective studies evaluating weight-based dosing of clindamycin and TMP/SMX in the setting of cellulitis are warranted.

Cxcr2 signaling and the microbiome suppress inflammation, bile duct injury, and the phenotype of experimental biliary atresia.

Biliary atresia is progressive fibro-inflammatory cholangiopathy of young children. Central to pathogenic mechanisms of injury is the tissue targeting by the innate and adaptive immune cells. Among these cells, neutrophils and the IL-8/Cxcl-8 signaling via its Cxcr2 receptor have been linked to bile duct injury. Here, we aimed to investigate whether the intestinal microbiome modulates Cxcr2-dependent bile duct injury and obstruction. Adult wild-type (WT) and Cxcr2-/- mice were fed a diet supplemented with sulfamethoxazole/trimethoprim (SMZ/TMP) during pregnancy and lactation, and their pups were injected intraperitoneally with rhesus rotavirus (RRV) within 24 hours of life to induce experimental biliary atresia. The maternal exposure to SMZ/TMP significantly lowered the incidence of jaundice and bile duct obstruction and resulted in improved survival, especially in Cxcr2-/- mice. Analyses of the microbiome by deep sequencing of 16S rRNA of the neonatal colon showed a delay in bacterial colonization of WT mice induced by SMZ/TMP, with a notable switch from Proteobacteria to Firmicutes. Interestingly, the genetic inactivation of Cxcr2 alone produced a similar bacterial shift. When treated with SMZ/TMP, Cxcr2-/- mice infected with RRV to induce experimental biliary atresia showed further enrichment of Corynebacterium, Anaerococcus and Streptococcus. Among these, Anaerococcus lactolyticus was significantly associated with a suppression of biliary injury, cholestasis, and survivability. These results suggest that the postnatal development of the intestinal microbiota is an important susceptibility factor for experimental biliary atresia.

Descriptivo de Hafnia alvei aisladas en coprocultivo: aproximación a su valoración en clínica / A descriptive study of Hafnia alvei isolated from stool samples: an approach to its clinical assessment

Introducción. El papel de Hafnia alvei en la etiología de diarrea en humanos es todavía muy controvertido; el objetivo del estudio fue describir la población en cuyos coprocultivos se aisló H. alvei y el manejo terapéutico de estos casos en nuestro Área de Salud. Material y métodos. Para ello se realizó un estudio descriptivo retrospectivo de 2014 y 2015. Se recogieron en la historia clínica informatizada, variables epidemiológicas, clínicas, tratamiento y evolución. Resultados. Se procesaron 7.290 coprocultivos, 3.321 en 2014, 58 (1,7%) en los que se aisló H. alvei y 3.969 en 2015, 53 (1,3%) positivos. El 60,4% de las muestras fueron aisladas en mujeres. La edad media fue de 38,68 años. El 68,5% provenían de Atención Primaria. En el 71,2% se recogió clínica asociada, siendo el más frecuente la diarrea en el 57,7%. En el 75,7% de los casos no existía patología de base asociada. El 43,2% de los casos recibió tratamiento de los cuales el 66,7% de los pacientes procedían de Atención Primaria. La duración media del tratamiento fue de 8 días. En el 85,4% de los casos tratados, la evolución fue favorable. Todas las cepas fueron sensibles a ciprofloxacino y trimetoprim/sulfametoxazol. Conclusiones. Faltan estudios que establezcan de forma concluyente la enteropatogenicidad o no de H. alvei (AU)

Introduction. The importance in human diarrhoeal disease of Hafnia alvei is unclear. The objective of the study was to describe the population which was isolated H. alvei in stool cultures and the therapeutic management of these cases in our Health Area. Material and methods. A descriptive retrospective study was carried out in 2014 and 2015. Epidemiological, clinical, treatment and evolution variables were collected in the computerized clinical history. Result. A collection of 7,290 stool specimens were processed, 3,321 in 2014 and 3,969 in 2015, of which 58 (1.7%) and 53 (1.3%) were positive for H. alvei, respectively. A 60.4% of samples were isolated in women. The mean age was 38.68 years. A 68.5% of samples were from primary care. In 71.2% there was related clinic, diarrhoea in 57.7%. In 75.7% of the cases there was not associated underlying disease. A 43.2% of the cases received treatment. A 66.7% of treated patients came from Primary Care. The mean duration of treatment was 8 days. The evolution was favourable in 85.4% of the cases treated. All strains were susceptible to ciprofloxacin and trimethoprim/sulfamethoxazole. Conclusions. More evidence is needed to support H. alvei as a cause of gastroenteritis (AU)

Neumonía por Burkholderia cepacia, ¿supone la cirrosis hepática un factor predisponente? / Is hepatic cirrhosis a predisposing factor for Burkholderia cepacia pneumonia?

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Pharmacokinetics of sulfamethoxazole and trimethoprim in Pacific white shrimp, Litopenaeus vannamei, after oral administration of single-dose and multiple-dose.

The tissue distribution and depletion of sulfamethoxazole (SMZ) and trimethoprim (TMP) were studied in Pacific white shrimp, Litopenaeus vannamei, after single-dose and multiple-dose oral administration of SMZ-TMP (5:1) via medicated feed. In single-dose oral administration, shrimps were fed once at a dose of 100 mg/kg (drug weight/body weight). In multiple-dose oral administration, shrimps were fed three times a day for three consecutive days at a dose of 100mg/kg. The results showed the kinetic characteristic of SMZ was different from TMP in Pacific white shrimp. In the single-dose administration, the SMZ was widely distributed in the tissues, while TMP was highly concentrated in the hepatopancreas. The t1/2z values of SMZ were larger and persist longer than TMP in Pacific white shrimp. In the multiple-dose administration, SMZ accumulated well in the tissues, and reached steady state level after successive administrations, while TMP did not. TMP concentration even appeared the downward trend with the increase of drug times. Compared with the single dose, the t1/2z values of SMZ in hepatopancreas (8.22-11.33h) and muscle (6.53-10.92h) of Pacific white shrimps rose, but the haemolymph dropped (13.76-11.03) in the multiple-dose oral administration. Meanwhile, the corresponding values of TMP also rose in hepatopancreas (4.53-9.65h) and muscle (2.12-2.71h), and declined in haemolymph (7.38-5.25h) following single-dose and multiple-dose oral administration in Pacific white shrimps. In addition, it is worth mentioning that the ratios of SMZ and TMP were unusually larger than the general aim ratio.