Are we witnessing a paradigm shift in leprosy: Two atypical presentations of histoid hansen's disease.

Hansen's disease is a chronic infectious granulomatous disease with varied clinical presentation. In the postelimination era, histoid Hansen's disease is an important emerging lepromatous subset known to mimic varied dermatoses, thereby making clinical diagnosis difficult and often delayed. We report two cases of histoid Hansen's disease bereft of clinical cardinal signs of leprosy.

Fish oil-supplemented parenteral nutrition could alleviate acute lung injury, modulate immunity, and reduce inflammation in rats with abdominal sepsis.

The objectives were to confirm that intravenous fish oil (FO) emulsions could alleviate acute lung injury, modulate immunity, and reduce inflammation in rats with abdominal sepsis and to explore the mechanisms of these effects. Thirty-six adult male Sprague-Dawley rats were divided into 4 groups randomly. Two days after central venous catheterization, rats were subjected to cecal ligation and puncture to produce abdominal sepsis. Rats were assigned to receive normal saline or total parenteral nutrition (TPN) containing standard soybean oil emulsions or FO-supplemented TPN at the onset of sepsis for 5 days. A sham operation and control treatment were performed in control group rats. Acute lung injury scores, peripheral blood lymphocyte subsets, plasma cytokines, and Foxp3 expression in the spleen were determined. Compared with the normal saline and TPN without FO, FO-supplemented TPN beneficially altered the distributions of the T-lymphocyte subsets and downregulated the acute lung injury scores, plasma cytokines, and expression of Foxp3 due to sepsis. Fish oil-supplemented TPN can decrease acute lung injury scores, alleviate histopathology, reduce the bacterial load in the peritoneal lavage fluid, modulate the lymphocyte subpopulation in the peripheral blood, downregulate Foxp3 expression in the spleen, and reduce plasma cytokines, which means that FO-supplemented TPN can alleviate acute lung injury, modulate immunity, and reduce inflammation in rats with abdominal sepsis.

Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid.

Bacterial infections of the lungs and abdomen are among the most common causes of sepsis. Abdominal peritonitis often results in acute lung injury (ALI). Recent reports demonstrate a potential benefit of parenteral vitamin C [ascorbic acid (AscA)] in the pathogenesis of sepsis. Therefore we examined the mechanisms of vitamin C supplementation in the setting of abdominal peritonitis-mediated ALI. We hypothesized that vitamin C supplementation would protect lungs by restoring alveolar epithelial barrier integrity and preventing sepsis-associated coagulopathy. Male C57BL/6 mice were intraperitoneally injected with a fecal stem solution to induce abdominal peritonitis (FIP) 30 min prior to receiving either AscA (200 mg/kg) or dehydroascorbic acid (200 mg/kg). Variables examined included survival, extent of ALI, pulmonary inflammatory markers (myeloperoxidase, chemokines), bronchoalveolar epithelial permeability, alveolar fluid clearance, epithelial ion channel, and pump expression (aquaporin 5, cystic fibrosis transmembrane conductance regulator, epithelial sodium channel, and Na(+)-K(+)-ATPase), tight junction protein expression (claudins, occludins, zona occludens), cytoskeletal rearrangements (F-actin polymerization), and coagulation parameters (thromboelastography, pro- and anticoagulants, fibrinolysis mediators) of septic blood. FIP-mediated ALI was characterized by compromised lung epithelial permeability, reduced alveolar fluid clearance, pulmonary inflammation and neutrophil sequestration, coagulation abnormalities, and increased mortality. Parenteral vitamin C infusion protected mice from the deleterious consequences of sepsis by multiple mechanisms, including attenuation of the proinflammatory response, enhancement of epithelial barrier function, increasing alveolar fluid clearance, and prevention of sepsis-associated coagulation abnormalities. Parenteral vitamin C may potentially have a role in the management of sepsis and ALI associated with sepsis.

Intra-abdominal Rhizopus microsporus infection successfully treated by combined aggressive surgical, antifungal, and iron chelating therapy.

SUMMARY: Zygomycetes are widely distributed in the environment as inhabitants of soil and decaying matter. On rare occasions, these organisms can cause invasive infections in immunocompromised hosts. As zygomycetes are resistant to most conventional antifungal agents, its infection is often fatal. We report 2 cases of unusual intra-abdominal Rhizopus microsporus infection in children with acute leukemia as a result of an unprecedented outbreak due to oral intake of contaminated allopurinol tablets and ready-to-eat food items. Among the 2 patients, one of them survived after aggressive combined surgical, antifungal (AmBisome, Caspofungin, and Posaconazole) and iron chelation therapy.

[Relationship between pigment gallstone and intestinal barrier function: experiment with guinea pigs and clinical observations].

OBJECTIVE: To investigate the relationship between the intestinal barrier function and pigment gallstone formation. METHODS: Ninety Guinea pigs were divided randomly into 3 groups: normal control (CON) group receiving normal forage, pigment gallstone (PS) group receiving pigment gallstone-forming forage, and intestinal mucosa protection group receiving pigment gallstone-forming forage with supplemental glutamine intestinal (GLN), a mucosa protector. The guinea pigs were observed for 8 weeks, the gallstone-forming rate, plasma diamine oxidase ( DAO), serum endotoxin, proportionality of urine lactulose/mannitol, and biliary beta-glucuronidase were detected. PCR was used to detect the bacteria in abdominal lymph node taking 16SrRNA as the target gene common in most bacteria. 32 gallstone patients, 16 with cholesterol gallstone and 16 with pigmental gallstone, and 27 patients with non-gastroenterological diseases, as controls, underwent detection of the plasma DAO and serum endotoxin. Another 109 gallstone patients, 31 with cholesterol gallstone and 78 with pigmental gallstone, and 21 patients with nongastroenterological diseases, as controls, underwent detection of urine technetium-labeled diethylenetriamine-pentaacetate (99mTc-DTPA). RESULTS: The gallstone-forming rate of the guinea pigs of the GLN group was 44.4% was, significantly lower than that of the PS group (73.9%, P < 0.05). The plasma DAO, serum endotoxin levels, proportionality of urine lactulose/mannitol, and activity of biliary beta-glucuronidase of the PS group were all significantly higher than those of the CON group (P < 0.05 or P < 0.01). The plasma endotoxin level of the pigmental GLN group was significantly lower than that of the PS group (P < 0.01). The positive rate of bacteria in abdominal lymph node of the PS group was 80%, significantly higher than those of the CON and GLN groups (30% and 45% respectively, P < 0.01 and P < 0.05). The level of plasma DAO and endotoxin of the pigmental gallstone patients were significantly higher than those of the controls (P < 0.05 and P < 0.01). The urine 99mTc-DTPA excretion rate of gallstone patients was 11.4%, significantly higher than that of the controls (4.7%, P < 0.01). CONCLUSION: Intestinal barrier function is correlated with pigment gallstone forming. Intestinal barrier function disorder may promote pigment gallstone formation through bacteria translocation, endotoxemia, and increase of biliary beta-glucuronidase.

Comparison of sequential intravenous/oral ciprofloxacin plus metronidazole with intravenous ceftriaxone plus metronidazole for treatment of complicated intra-abdominal infections.

BACKGROUND AND PURPOSE: Intra-abdominal infections are a substantial clinical problem and an important cause of morbidity and death in the hospital. Optimal treatment requires both source control and antibiotic therapy. Sequential intravenous (IV) to oral therapy may improve patient convenience and reduce total health care costs. In this randomized, double-blind trial, the efficacy of sequential IV-to-oral ciprofloxacin plus metronidazole was compared with ceftriaxone plus metronidazole in adult patients with complicated intra-abdominal infections. METHODS: The trial enrolled 531 patients, who began with IV therapy. Patients who improved clinically were switched to oral therapy on day three or later. The clinical and bacteriological responses four to six weeks after the end of therapy and the safety of the two regimens were assessed. To maintain blinding, the patients received placebo IV in the ciprofloxacin group or placebo orally in the ceftriaxone group. A total of 475 patients (235 ciprofloxacin plus metronidazole, 240 ceftriaxone plus metronidazole) were valid for evaluation of efficacy. All patients were included in the safety analysis. RESULTS: Of the patients valid for efficacy, 78% of the ciprofloxacin plus metronidazole group and 81% of the ceftriaxone plus metronidazole group were eligible for a switch to oral therapy. The clinical success rates were 98.9% and 96.9%, respectively, which were statistically equivalent. The clinical success rates for all patients, including those on continuous IV therapy, were 90.6% and 87.9%. Source control was achieved in more than 90% of the patients. The bacteriological eradication rates were similar in the two groups. Bacterial complications (e.g., surgical site infections, abscesses) were encountered more often in the ceftriaxone plus metronidazole group. CONCLUSIONS: Sequential ciprofloxacin plus metronidazole IV-to-oral therapy was statistically equivalent to ceftriaxone plus metronidazole. The switch to oral therapy with ciprofloxacin plus metronidazole was as effective and safe as continued IV therapy in patients able to tolerate enteral feeding.

Addition of Maitake D-fraction reduces the effective dosage of vancomycin for the treatment of Listeria-infected mice.

Maitake D-fraction, beta1,6-glucan having beta1,3-branches, has been reported to activate the immune system of the host. To elucidate whether the D-fraction can reduce the clinical effective dosage of antibiotics in the treatment of opportunistic bacterial infection, we examined the effects of D-fraction on the treatment of Listeria monocytogenes-infected mice in combination with vancomycine (VCM), the only antibiotic used for methicillin-resistant Staphylococcus aureus (MRSA). Listeria-infection was introduced by its inoculation into the abdominal cavity of mice. Without treatment, all inoculated mice died within 3 days after the inoculation. In contrast, in the mice treated with combined therapy of D-faction (10 mg/kg per day) and VCM (10 mg/kg per day), the survival rate was maintained at 60% on the 10th day after the inoculation, which was superior to that of mice treated with VCM alone (10 mg/kg per day). To investigate the mechanism underlying the reinforcement of VCM treatment by the D-fraction, the activities of macrophages and splenic T cells of Listeria-infected mice were evaluated. In mice administered with both D-fraction and VCM, macrophages produced 2.7 times as much interleukin-1 as that of non-treated control mice. The bactericidal activity of splenic T cells was also enhanced by 2.6 times of that of non-treated control mice. These results indicate that D-fraction activates immuno-competent cells, induced cytokine production, and consequently enhanced the bactericidal activities of the splenic T cells against Listeria monocytogenes, suggesting the clinical benefit of D-fraction in the case of anti-bacterial treatment for patients with high risks.

Antimicrobial therapy for intraabdominal infection.

Timely and appropriate antimicrobial therapy is an essential component of the management of intraabdominal infection. Over the past three decades, our ability to treat these infections optimally has been enhanced by an increased understanding of the underlying microbial pathogens, by the development of new antimicrobial agents, and by the completion of several well-controlled clinical trials that guide treatment. This article provides an overview of the approach to antimicrobial therapy in patients with intraabdominal infection. A literature review was performed to collect the information used in this article. Data were derived from experimental and clinical studies evaluating the microbiology and treatment of intraabdominal infections. Evidence from both animal studies and clinical trials supports the initiation of empiric antimicrobial therapy directed against Escherichia coli and other common members of the family Enterobacteriaceae, as well as the anaerobe Bacteroides fragilis. Based on this premise, the clinician is faced with a broad selection of possible single agents, as well as combinations of agents that fulfill these criteria. The factors involved in selecting a specific regimen include consideration of the antimicrobial spectrum of various agents, experimental animal studies evaluating their efficacy, and, importantly, efficacy in well-designed clinical trials. In addition, consideration of safety profiles, pharmacokinetics, and cost of specific pharmaceutical agents should be made when selecting a regimen. Antimicrobial therapy is an important component of the management of intraabdominal infection. The results of well-designed clinical trials evaluating various aspects of therapy should serve to guide treatment.

A comparison of imipenem/cilastatin with the combination of cefuroxime and metronidazole in the treatment of intra-abdominal infections.

515 patients with intra-abdominal infection participated in an open randomized comparative multicenter trial in order to compare the efficacy, safety, and tolerance of imipenem/cilastatin with cefuroxime/metronidazole. 258 patients (mean age 56 years) received imipenem/cilastatin 1.5-2.0 g/day, and 257 patients (mean age 54 years) received cefuroxime 3.0-4.5 g/day plus metronidazole 1.0-1.5 g/day for at least 3 days. 130/161 evaluable patients (80.8%) receiving imipenem/cilastatin and 124/145 evaluable patients (85.5%) receiving cefuroxime/metronidazole were clinically cured. The microbiological response was favorable in 86.9% in the imipenem/cilastatin group and in 90.8% in the cefuroxime/metronidazole group. The two treatment groups were similar with respect to median time to defervescence which was 4 days. The median duration of treatment was 6 days and the median time to discharge from hospital was 9 days in both groups. Drug-related adverse reactions were observed in 14 patients receiving iminpenem/cilastatin and in 8 patients receiving cefuroxime/metronidazole. 19 patients in the imipenen/cilastatin group and 12 patients in the cefuroxime/metronidazole group died. No correlation was found between the deaths and the study drugs. The present study shows that intra-abdominal infections can be treated successfully with imipenem/cilastatin as well as with cefuroxime/metronidazole.

Cephalosporin-metronidazole combinations in the management of intra-abdominal infections.

With our current understanding of antimicrobial pharmacokinetics and pharmacodynamics, optimal antimicrobial dosing strategies can be developed for a variety infectious processes. Herein, we discuss the clinical utility of a combination containing a third-generation cephalosporin plus metronidazole as compared to conventional single agents (cefoxitin and ampicillin-sulbactam) for the management intra-abdominal infections. At present, several studies have been performed that compare the bactericidal activity of such combinations to that of single agents for organisms commonly isolated from these intra-abdominal process. From these studies it appears that the use of a third-generation cephalosporin with strong activity against common aerobic organisms associated with intra-abdominal infections in combination with a potent anaerobic drug such as metronidazole provides improved antibacterial activity and optimizes the pharmacodynamic profile of the agents over the dosing interval compared to conventional single agents. As a result of the pharmacokinetic and pharmaco-dynamic superiority of the combination regimen, considerable pharmacoeconomic advantages may be realized with the clinical implementation of a third-generation cephalosporin plus metronidazole regimen. This approach should result in maximal clinical efficacy and is important not only for individual patient therapy, but also for formulary management decisions.

Biapenem versus imipenem in the treatment of experimental intraabdominal infections.

A reproducible experimental model of intraabdominal infections in rats has been devised in order to simulate intraabdominal infections in patients. The experimental model was used to compare the efficacy of biapenem with imipenem. Three groups of animals were used, each group consisting of 20 animals. Antibacterial agents were given by injection initially 1 h after surgery and then at 12 h intervals for 12 days. The drugs and amounts of agents given per dose were biapenem 10 mg and imipenem 10 mg, respectively. The control group received 0.9% sterile saline. 80% of the untreated animals died within 3 days. Animals treated with biapenem or imipenem had a significantly decreased mortality and increased cure rates during the experimental period. Only two animals in the two treatment groups died. Biapenem seems to be useful in the treatment of intraabdominal infections.

Susceptibility of intra-abdominal isolates at operation: a predictor of postoperative infection.

Antimicrobial resistance of operative site flora was correlated with postoperative infection in 175 patients undergoing operation for intra-abdominal sepsis: Diagnoses for study patients were acute or gangrenous appendicitis in 48 (27%), complicated appendicitis in 98 (56%), perforated viscus other than appendix in 21 (12%), and eight (5%) had other intra-abdominal infections. One hundred thirty-six (78%) patients were males. The average age was 33 +/- 14 years, average number of hospital days was 11.6 +/- 13.5, and average number of days on antibiotics was 6.9 +/- 2.5. Overall recovery without infection was 75 per cent (131/175). Analysis of susceptibility of 939 intraoperative isolates indicated a significant relationship (P = 0.0002) between resistance to the empiric antimicrobials received and postoperative infection. Of 131 patients with resolution of the intra-abdominal infection, 57 (44%) had resistant isolates while 36 (82%) of 44 patients with postoperative infectious complications had resistant isolates. Streptococcus Group D, Escherichia coli, and Bacteroides fragilis were the most prevalent resistant organisms isolated from both intra- and postoperative cultures. Other variables that were significantly different between those without complications and those who had complications were, respectively: average age 31 versus 38; admission WBC 14.5 versus 16.7; and diagnosis, acute appendicitis 28 per cent versus 2 per cent. A stepwise logistic regression analysis confirmed the predictive value of intraoperative isolate resistance, age, and admission WBC, in that order, on outcome.

Treatment of recalcitrant actinomycosis with ciprofloxacin.

We describe a case of actinomycosis with several unusual features. The patient has been under medical supervision for more than 20 years; the disease has spread in an atypical manner and did not respond to standard therapy. Finally, there has been an unexpected response to a prolonged course of a member of the quinolone group of antibiotics.

Use of cephalosporins for prophylaxis and therapy of polymicrobial infection in mice.

Cefoxitin, cefotetan, and cefmetazole were compared in 10-day therapy of intra-abdominal and subcutaneous infections caused by three organisms: Bacteroides fragilis and Bacteroides thetaiotaomicron combined with either Escherichia coli or Staphylococcus aureus. Intra-abdominal infection was caused by B. fragilis plus B. thetaiotaomicron plus E. coli. Therapy was initiated immediately before inoculation or was delayed for 8 h. Mortality was 14 of 30 (47%) for saline-treated mice, and all survivors developed abscesses. Immediate therapy reduced mortality and the percentage of mice with abscesses (in survivors), respectively, to 17 and 20% with cefoxitin, 0 and 13% with cefotetan, and 0 and 17% with cefmetazole, and the numbers of all bacteria were reduced by all the cephalosporins. Delayed therapy reduced mortality and abscess formation, respectively, to 20 and 8% of mice with cefoxitin, 10 and 93% with cefotetan, and 7 and 96% with cefmetazole. B. thetaiotaomicron survived in all abscesses treated with cefotetan and cefmetazole. Subcutaneous abscesses were caused by each organism alone or in combinations of one aerobe (S. aureus or E. coli) and one or two Bacteroides species. Early therapy reduced the numbers of all bacteria independent of their in vitro susceptibility. All agents reduced the number of each Bacteroides species with either E. coli or S. aureus. However, when therapy was delayed, cefotetan and cefmetazole were less effective than cefoxitin against B. thetaiotaomicron. Cefotetan was the most active agent against E. coli, and cefmetazole was the most effective against S. aureus. These data illustrate the efficacy of all tested cephalosporins in the prophylaxis of polymicrobial infections.

Phospholipid impregnation of abdominal rubber drains: resistance to bacterial adherence but no effect on drain-induced bacterial translocation.

In order to evaluate the effect of surface modification of biomaterials on bacterial adherence and bacterial translocation after intraperitoneal biomaterial implantation, phosphatidylcholine- or phosphatidylinositol-impregnated rubber drain pieces, which had been intraperitoneally implanted in the rat for 2 and 7 days, or unimplanted, were incubated in vitro with 3H-labelled Escherichia coli and Enterobacter cloacae. As compared with unimpregnated pieces, the adherence of bacteria significantly decreased to phosphatidylcholine- and phosphatidylinositol-impregnated rubber drain pieces that were either unimplanted or implanted for 2 days, but not for 7 days. The supplementation of albumin in the medium reduced the adherence of bacteria to the unimplanted, unimpregnated drain pieces, but did not further decrease adherence of bacteria to the unimplanted, phospholipid-impregnated brain pieces. Bacterial growth was inhibited after incubation in nutrient broth supplemented with phospholipids. The incidence of enteric bacterial translocation induced by intraperitoneal drain implantation did not differ between phospholipid-impregnated and unimpregnated drain pieces. Scanning electron microscopy revealed a large amount of biofilm and fibrous deposition on the surface of the implanted, phospholipid-impregnated rubber drain pieces. Thus, phospholipid impregnation of rubber drains reduces bacterial adherence and inhibits bacterial growth, without influencing the incidence of bacterial translocation.