Ofloxacin plus Rifampicin versus Doxycycline plus Rifampicin in the treatment of brucellosis: a randomized clinical trial [ISRCTN11871179]

BACKGROUND: The combination therapies recommended by the World Health Organization for treatment of brucellosis are doxycycline plus rifampicin or doxycycline plus streptomycin. Although highly successful results have been obtained with these two regimens, relapse rates as high as 14.4%. The most effective and the least toxic chemotherapy for human brucellosis is still undetermined. The aim of the present study was to investigate the efficacy, adverse effects and cost of ofloxacin plus rifampicin therapy, and doxycycline plus rifampicin therapy and evaluate in the treatment of brucellosis. METHODS: The open trial has been carried out prospectively by the two medical centers from December 1999 to December 2001 in Duzce region Turkey. The diagnosis was based on the presence of signs and symptoms compatible with brucellosis including a positive agglutination titre (≥1/160) and/or a positive culture. Doxycycline and rifampicin group consisted of 14 patients who were given doxycycline 200 mg/day plus rifampicin 600 mg/day during 45 days and this group Ofloxacin plus rifampicin group was consisted of 15 patients who were given ofloxacin 400 mg/day plus rifampicin 600 mg/day during 30 days. RESULTS: Regarding clinical and/or demographic characteristics no significant difference was found between two groups of patients that underwent two different therapeutic regimens. At the end of the therapy, two relapses were seen in both groups (p = 0.695). Although duration of therapy was two weeks shorter in group treated with rifampicin plus ofloxacin, the cure rate was similar in both groups of examinees. Fever dropped more rapidly in the group that treated with rifampicin plus ofloxacin, 74 ± 30 (ranges 48–216) vs. 106 ± 26 (ranges 48–262) hours (p = 0.016). CONCLUSIONS: Ofloxacin plus rifampicin therapy has advantages of shorter treatment duration and provided shorter course of fever with treatment than in doxycycline plus rifampicin therapy. However, cost of ofloxacin plus rifampicin treatment is higher than doxycycline plus rifampicin treatment. Because of the similar effects, adverse effects and relapses rates between two regimens, we still advice doxycycline plus rifampicin for the treatment of brucellosis for countries, which have limited resources

Estudo da formação de aderências e da cicatrização de anastomoses colônicas em ratos com sepse peritoneal induzida

OBJETIVO: Avaliar os efeitos da sepse abdominal sobre a formação de aderências e a cicatrização de anastomoses colônicas em ratos. MÉTODOS: 40 ratos distribuídos em dois grupos contendo 20 animais, para anastomose do cólon esquerdo na presença (grupo S) ou ausência (grupo N) de indução de sepse por ligadura e punção do ceco (CLP). Cada grupo foi dividido em subgrupos para eutanásia no terceiro (N3 e S3) ou sétimo (N7 e S7) dia de pós-operatório (DPO). Foi avaliada a quantidade de aderências e removido um segmento colônico contendo a anastomose para análise histopatológica, força de ruptura, hidroxiprolina e conteúdo de colágeno tecidual. RESULTADOS: Os animais submetidos à CLP apresentaram maior quantidade de aderências intra-abdominais tanto no 3° DPO (p=0,00) quanto no 7° DPO (p=0,00). Tiveram menores valores de força de ruptura no 3° DPO (p=0,00), porém maiores valores no 7° DPO (p=0,00). Não houve diferença na variação da concentração de hidroxiprolina, conteúdo de colágeno e histopatologia. CONCLUSÕES: A infecção peritoneal desencadeada por CLP aumentou a quantidade de aderências intra-cavitárias. Houve diminuição da resistência de anastomoses cólicas no 3° DPO, com posterior aumento no 7° DPO, sem efeito sobre os outros parâmetros da cicatrização. ________________________________________________________________________________ ABSTRACTPURPOSE: To evaluate the effects of abdominal sepsis on adhesion formation and colon anastomosis healing in rats. METHODS: Forty rats were distributed in two groups containing 20 rats each for left colon anastomosis in the presence (Group S) or absence (Group N) of induced sepsis by cecal ligation and puncture. Each group was divided into subgroups for euthanasia on the third (N3 and S3) or seventh (N7 or S7) post-operative day. The amount of adhesions was evaluated and a segment of the colon was removed for histopathologic analysis, bursting strength assessment, hydroxyproline and the determination of tissue collagen. RESULTS: The subjects which underwent cecal ligation and puncture presented a higher amount of intra-abdominal adherences in both third (p=0,00) and seventh (p=0,00) post-operatory days. Smaller bursting strengths were found in the S3 subgroup, and greater bursting strengths were found in the S7 subgroup. There was no difference in the variations on the concentrations of hydroxyproline, tissue collagen and histopathology. CONCLUSIONS: The peritoneal infection which was developed by cecal ligation and puncture raised the amount of intra-cavitary adhesions. There was a decrease in the amount of colonic anastomosis on the third post-operatory day with a following raise on the seventh without any effects on other healing parameters

Systematic Review and Meta-Analysis of Randomized Clinical Trials in the Treatment of Human Brucellosis

BACKGROUND: Brucellosis is a persistent health problem in many developing countries throughout the world, and the search for simple and effective treatment continues to be of great importance. METHODS AND FINDINGS: A search was conducted in MEDLINE and in the Cochrane Central Register of Controlled Trials (CENTRAL). Clinical trials published from 1985 to present that assess different antimicrobial regimens in cases of documented acute uncomplicated human brucellosis were included. The primary outcomes were relapse, therapeutic failure, combined variable of relapse and therapeutic failure, and adverse effect rates. A meta-analysis with a fixed effect model was performed and odds ratio with 95% confidence intervals were calculated. A random effect model was used when significant heterogeneity between studies was verified. Comparison of combined doxycycline and rifampicin with a combination of doxycycline and streptomycin favors the latter regimen (OR = 3.17; CI95% = 2.05-4.91). There were no significant differences between combined doxycycline-streptomycin and combined doxycycline-gentamicin (OR = 1.89; CI95% = 0.81-4.39). Treatment with rifampicin and quinolones was similar to combined doxycycline-rifampicin (OR = 1.23; CI95% = 0.63-2.40). Only one study assessed triple therapy with aminoglycoside-doxycycline-rifampicin and only included patients with uncomplicated brucellosis. Thus this approach cannot be considered the therapy of choice until further studies have been performed. Combined doxycycline/co-trimoxazole or doxycycline monotherapy could represent a cost-effective alternative in certain patient groups, and further studies are needed in the future. CONCLUSIONS: Although the preferred treatment in uncomplicated human brucellosis is doxycycline-aminoglycoside combination, other treatments based on oral regimens or monotherapy should not be rejected until they are better studied. Triple therapy should not be considered the current treatment of choice

Effect of granulocyte-colony stimulation factor on peritoneal defense mechanisms and bacterial translocation after administration of systemic chemotherapy in rats

PubMed: 17552008Aim: To investigate the effects of granulocyte-colony stimulating factor (G-CSF) on peritoneal defense mechanisms and bacterial translocation after systemic 5-Fluorouracil (5-FU) administration. Methods: Thirty Wistar albino rats were divided into three groups; the control, 5-FU and 5-FU + G-CSF groups. We measured bactericidal activity of the peritoneal fluid, phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid, total peritoneal cell counts and cell types of peritoneal washing fluid. Bacterial translocation was quantified by mesenteric lymph node, liver and spleen tissue cultures. Results: Systemic 5-FU reduced total peritoneal cell counts, neutrophils and macrophage numbers. It also altered bactericidal activity of the peritoneal fluid and phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid. 5-FU also caused significant increase in frequencies of bacterial translocation at the liver and mesenteric lymph nodes. G-CSF decreased bacterial translocation, it significantly enhanced bactericidal activity of the peritoneal fluid and phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid. It also increased total peritoneal cell counts, neutrophils and macrophage numbers. Conclusion: Systemic 5-FU administration caused bacterial translocation, decreased the bactericidal activity of peritoneal fluid and phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid. G-CSF increased both bactericidal activity of the peritoneal fluid and phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid, and prevented the bacterial translocation. We conclude that intraperitoneal GCSF administration protects the effects of systemic 5-FU on peritoneal defense mechanisms. © 2007 The WJG Press. All rights reserved

The effect of G-CSF in an experimental MRSA graft infection in mice

Eurosurgery 2000 Meeting -- JUN 21-24, 2000 -- ISTANBUL, TURKEYWOS: 000233300500003PubMed: 16249165Wound infection after prosthetic material implantation is a troublesome complication with an incidence of 2% to 10%. The effect of granulocyte colony-stimulating factor (G-CSF) was studied in an experimental methicillin-resistant Staphylococcus aureus (MRSA) graft infection model. Eighty adult mice were used. Under general anesthesia an abdominal incision of 2 cm in length was performed. A subcutaneous cavity of 2 x 2 cm in size was created. Polypropylene mesh pieces of 2 x 1 cm and MRSA solution of 0.1 ml of 10(8) CFU/mL were used. G-CSF was applied systemically or locally in a dosage of 0.02 MU/30 g body weight. There were 8 groups: group I, wound + MRSA; group II, wound + mesh + MRSA; group III, wound + mesh + MRSA + G-CSF (ip, 48 h before operation); group IV, wound + mesh + MRSA + G-CSF (ip, 24 h before operation); group V, wound + mesh + MRSA + G-CSF (locally, into the cavity); group VI, wound + mesh (incubated in G-CSF solution for 4 h) + MRSA; group VII, wound + mesh + MRSA + G-CSF, ip, 24 h from operation; and group VIII (positive control group), wound + mesh + MRSA + Teicoplanin (0.03 mg/30 g body weight, ip, 1/2 h before operation). Three days after, animals were killed and incisions were examined for possible infection or abscess formation and wound failure. Meshes were removed; after vortexing and dilution, samples were incubated with 5% agar media. Results of bacterial incubation were evaluated 24 h and 48 h later. There were symptoms of wound infection and abscess formation in all groups except group VIII. In group VIII, MRSA was isolated in 7 events with a colony count below 10(3). Bacterial counts were above 106 (10(6)-10(8)) in all other groups. Thus, it was observed that wound infection could be created with this model, but G-CSF could not prevent the development of wound infection, whether it was administered systemically or locally. Teicoplanin decreased the number of colony-forming units of MRSA, and prevents wound infection in this MRSA wound infection model

chemotherapy in rats

AIM: To investigate the effects of granulocyte-colony stimulating factor (G-CSF) on peritoneal defense mechanisms and bacterial translocation after systemic 5-Fluorouracil (5-FU) administration

Gold and gold-palladium coated polypropylene grafts in a S-epidermidis wound infection model

WOS: 000235771200010PubMed: 16139304Background. The use of non-absorbable mesh grafts in both abdominal wall defects and inguinal hernias are impossible in the presence of contamination. This study was conducted for evaluation of the efficiencies of polypropylene mesh grafts coated with gold and palladium-gold. Materials and methods. Ten piece of 1 x 2 cm. of polypropylene mesh grafts were used in each group of naive, gold-coated, and palladium-gold-coated. The grafts were incubated in physiological saline buffered and 0.5 McFarland slime positive Staphylococcus epidermidis for 24 h. At intervals of 6,12,24,48, 72 h grafts were washed with saline and vortexed for 2 min in 2 ml of physiological saline. There were 100 mu l of samples of vortexed material incubated in blood agar and 24 h later, colony numbers were assessed. In the second part of study, the grafts were implanted below the musculoaponeurotic layer at inguinal. region of rats following the same procedure of incubation and washing. On the 8th day, the rats were examined for infection rate and their wound cultures were obtained. Results. The least amount of bacterial growth was detected in the samples obtained from gold-palladium coated grafts; whereas the highest rate of growth was found in samples of naive grafts. The superficial surgical site infection rate was 0% in gold-palladium coated, 30% in gold-coated and 100% in naive polypropylene group. The bacterial growth rate from wound cultures confirmed the superficial surgical site infection rates in all groups. Conclusion. Prosthetic graft infection with S. epidermidis can be prevented by coating the graft with gold-palladium or gold. (c) 2006 Elsevier Inc. All rights reserved

A rat model of polypropylene graft infection caused by Staphylococcus epidermidis

WOS: 000237738500023PubMed: 16768701Background: The aim of this study was to constitute a valid graft infection model with Staphylococcus epidermidis in rats. Method: Rats were divided into seven groups. In groups 1 and 2, 2 cm x 2 cm polypropylene grafts were incubated with 10(8) c.f.u./mL slime-positive S. epidermidis at 37 degrees C for 2 and 24 h and were then placed subfascially to the groins of rats. In the third group, naive grafts were placed and 0.5 mL of 3 x 10(7) c.f.u. slime-positive S. epidermidis were injected on the inside of the wounds. Rifampicin (30 mg/kg) in group 4 and teicoplanin (20 mg/kg) in group 5 were applied i.p. to rats with 2-h incubated grafts for prophylaxis. The same prophylactic regimens were given to groups 6 and 7 in which rats were incubated for 24 h. At eighth day, rats were killed and wounds were assessed with macroscopic evaluation and cultures. Results: No death occurred in any of the groups. In groups 1 and 2, 100% infection rates were achieved. However, graft infection was detected in only two (20%) of the rats in group 3 (P = 0.001). Prophylactic application of teicoplanin or rifampicin decreased the infection rates significantly in the short-incubation groups. Conclusion: Incubation of polypropylene grafts with slime-producing S. epidermidis for 2 and 24 h in the pre-application period achieved the occurrence of a standardized graft infection. Prophylactic use of teicoplanin and rifampicin decreased the infection rates. We propose to use this reproducible and reliable animal model of graft infection in future studies

Effect of granulocyte-colony stimulation factor on peritoneal defense mechanisms and bacterial translocation after administration of systemic chemotherapy in rats

Aim: To investigate the effects of granulocyte-colony stimulating factor (G-CSF) on peritoneal defense mechanisms and bacterial translocation after systemic 5-Fluorouracil (5-FU) administration. Methods: Thirty Wistar albino rats were divided into three groups; the control, 5-FU and 5-FU + G-CSF groups. We measured bactericidal activity of the peritoneal fluid, phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid, total peritoneal cell counts and cell types of peritoneal washing fluid. Bacterial translocation was quantified by mesenteric lymph node, liver and spleen tissue cultures. Results: Systemic 5-FU reduced total peritoneal cell counts, neutrophils and macrophage numbers. It also altered bactericidal activity of the peritoneal fluid and phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid. 5-FU also caused significant increase in frequencies of bacterial translocation at the liver and mesenteric lymph nodes. G-CSF decreased bacterial translocation, it significantly enhanced bactericidal activity of the peritoneal fluid and phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid. It also increased total peritoneal cell counts, neutrophils and macrophage numbers. Conclusion: Systemic 5-FU administration caused bacterial translocation, decreased the bactericidal activity of peritoneal fluid and phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid. G-CSF increased both bactericidal activity of the peritoneal fluid and phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid, and prevented the bacterial translocation. We conclude that intraperitoneal GCSF administration protects the effects of systemic 5-FU on peritoneal defense mechanisms. © 2007 The WJG Press. All rights reserved

Staged abdominal repair for treatment of moderate to severe secondary peritonitis

WOS: 000227179000023PubMed: 15645335The aim of this study was to evaluate the effects of planned relaparotomy and to assess factors that may contribute to mortality in patients with moderate to severe secondary peritonitis. A total of 36 consecutive patients with an Acute Physiologic and Clinical Health Evaluation (APACHE) II score of >10 were enrolled the study for a 2-year period. The mean age of the patients was 56 years (17-92 years), and 23% of them were male. One-third of them had postoperative peritonitis; 152 scheduled operations were done, and the overall mortality rate was 36%. For patients whose septic source was in the upper gastrointestinal system, control of the source was more difficult (p = 0.004). Overall, 28 complications developed in 61% of the patients. Initial and second-day APACHE II scores were 14.5 (11-27) and 12.0 (9-25), respectively. The initial APACHE II score of survivors was lower than that of nonsurvivors [p = 0.0001, 95% confidence interval (CI) -9.5, -3.6]. Second-day APACHE II scores were not different (p = 0.19; 95% Cl -3.79, 0.80). Striking end or lateral duodenal leaks were clearly associated with high mortality. It is found that the initial APACHE II score, the success of controlling the source, the occurrence of complications, and the type of illness are independent factors that may affect mortality. We concluded that staged abdominal repair should be used with caution in the treatment of lateral or end duodenal leaks. It is a good alternative to conventional laparotomy for moderate to severe forms of secondary peritonitis from other sources