Evaluation of the efficacy of enrofloxacin in rainbow trout (Oncorhynchus mykiss) following experimental challenge with Yersinia ruckeri.

BACKGROUND: Use of enrofloxacin in trout farms is reported, especially for the treatment of yersiniosis, albeit various dosing regimens have been used. Therefore, optimal doses should be investigated. METHODS: Five groups of 15 fish were challenged with Y. ruckeri. Two days later, three groups received feed containing enrofloxacin (ENR) at 1, 2.5 and 5 mg/kg fish respectively, during 7 days; one group received a single intraperitoneal injection of ENR at 10 mg/kg; and one group was left untreated. On day 15, surviving fish were euthanized. RESULTS: All fish survived in the group treated by injection, compared to 53%, 60% and 40% of the fish treated with 1, 2.5 and 5 mg/kg oral ENR, respectively, and 53% in the infected untreated group. CONCLUSION: A single intraperitoneal injection of ENR at 10 mg/kg seems more relevant than repeated oral administrations. The ENR oral doses used in trout farms should be revised.

Effects of Greek juniper (Juniperus excelsa) extract on immune responses and disease resistance against Yersinia ruckeri in rainbow trout (Oncorhynchus mykiss).

This study investigated the effects of Greek juniper extract on immune responses of rainbow trout. In this experiment, 4 doses [0 (Control), 1 (J1), 4 (J4) and 8 (J8) mg/kg] of the extract were administered orally using an oral gavage twice a day for 14 days. Immune responses were measured on 7th and 14th days. On 14th day, Yersinia ruckeri was injected intraperitoneally to all fish of all groups. On 14th day, ORP in fish of J1 group increased significantly. Lysozyme activity (LA) was increased in J8 group on 7th day (p < .05). On 14th day, a significant decrease was determined in J1 and J4 treatments in LA. Myeloperoxidase activity was significantly decreased in all groups irrespective of sampling times (p < .05). Interleukin (IL)-1ß was significantly elevated in fish of J8 group on 7th day. IL-8 increased in fish of J8 and J4 groups on 7th day of the study. IL-12 gene expression was significantly up-regulated in J8 fish group on 7th day, and in J4 fish group on 14th day. Survival rate was higher in J8 treatment compared to the control and other treatments (p < .05). The results suggest that Juniperus excelsa provides protection against Y. ruckeri in rainbow trout.

Protective effect of in-feed specific IgM towards Yersinia ruckeri in rainbow trout.

Tightened regulations and an environmentally friendly approaches in fish production have greatly reduced the use of antibiotics but green solutions are continuously being explored. The use of functional feed may have a potential in the aquaculture sector in securing biomass and minimizing the loss from disease. In the present study, we tested the concept that blood from the fish slaughterhouse can be used for mass purification of specific antibodies which subsequently can be used for feeding fish and thereby confer protection against diseases. IgM was purified from serum from Yersinia ruckeri vaccinated rainbow trout and an IgM sandwich ELISA was developed for quantification of rainbow trout IgM. The purified IgM was encapsulated in alginate microparticles and top-coated in fish feed. IgM re-extracted from the alginate microparticles was shown to retain high reactivity towards Y. ruckeri antigens indicating that its bioactivity remained intact after encapsulation. IgM release from the alginate microparticles was only observed at high pH (pH 8.2) and minimal at low pH, indicating protection of IgM at low pH in the fish stomach during passage. In a feeding - challenge experiment (feeding 1 week before Y. ruckeri challenge and for two weeks following challenge), a statistically non-significant 10% lower mortality was observed in the high dose (400 µg IgM/fish/day fed over 3 weeks) group.

Antimicrobial therapy of acute diarrhoea: a clinical review.

Diarrhoea is one of the most commonly occurring diseases. This article presents a review of the current state of the treatment of acute infectious diarrhoea, as well as of the most important pathogens. The general principles of the therapy of diarrhoea are exemplified, followed by a description of the targeted antimicrobial therapy of the most important bacterial gastrointestinal infections, including salmonellosis, shigellosis and Campylobacter infections, as well as infections with pathogenic Escherichia coli strains, yersiniosis and cholera. Diarrhoea caused by toxigenic Clostridium difficile strains has increased in incidence and in severity. These infections will therefore be described in detail, including important new aspects of treatment. Symptomatic therapy is still the most important component of the treatment of infectious diarrhoea. However, empirical antibiotic therapy should be considered for severely ill patients with a high frequency of stools, fever, bloody diarrhoea, underlying immune deficiency, advanced age or significant comorbidities. Increasing resistance, in particular against fluoroquinolones, must be taken into consideration. Therapy with motility inhibitors is not recommended for Shiga toxin-producing Escherichia coli (STEC) infections, Clostridium difficile infections (CDI), and severe colitis. The macrocyclic antibiotic fidaxomicin can reduce the rate of recurrent disease in CDI. Furthermore, evidence for the benefits of faecal microbiota transplantation as a treatment option for multiple recurrences of CDI is increasing. In conclusion, the treatment of acute diarrhoea is still primarily supportive. General empirical antibiotic therapy for acute diarrhoea is not evidence-based.

Yersinia Enterocolitica Bacteremia in a Chronic, Mildly Iron-Overloaded Dialysis Patient.

OBJECTIVE: To report an unusual case of Yersinia enterocolitica in a chronic, mildly iron-overloaded dialysis patient lacking other typical risk factors for bacteremia, who was treated successfully with a third-generation cephalosporin as monotherapy for a short duration of treatment. CASE SUMMARY: A 76-year-old dialysis-dependent man developed Y. enterocolitica bacteremia after 8 days of hospitalization. One month prior to presentation, his ferritin level was mildly elevated at 571.5 ng/mL, while receiving both intravenous and oral iron supplements. On day 14 of hospitalization, his ferritin level was acutely increased to 885.8 ng/mL. No risk factors commonly associated with Yersinia were present. He was treated successfully with a 14-day course of intravenous ceftriaxone, with negative surveillance blood cultures 2 months after treatment. One year after the infection, there was no evidence of recurrence, despite reinitiation of intravenous iron therapy, albeit with lower ferritin levels. DISCUSSION: Y. enterocolitica is most commonly associated with patients receiving deferoxamine mesylate or those with iron overload, as the bacteria thrive in the presence of chelated iron. There has been limited experience with the use of third-generation cephalosporins as monotherapy for the treatment of Y. enterocolitica bacteremia; most of the data are from in vitro studies. Historical treatment choices have included aminoglycosides, doxycycline, trimethoprim/ sulfamethoxazole, and ciprofloxacin. Ceftriaxone was used in our patient because of the once-daily ease of administration, with complete resolution of bacteremia. Reinitiation of intravenous iron therapy, while keeping the ferritin levels below 300 ng/mL, allowed for treatment of his anemia without recurrence of infection. CONCLUSIONS: This is the first English-language case of a dialysis patient with mild iron overload leading to Y. enterocolitica, despite having no known risk factors for the infection. Treatment success was obtained after a 14-day course of intravenous ceftriaxone. Intravenous iron was restarted without recurrence of infection, underscoring the importance of monitoring iron status in chronic dialysis patients.

Albomycin is an effective antibiotic, as exemplified with Yersinia enterocolitica and Streptococcus pneumoniae.

Albomycin belongs to the class of sideromycins, compounds composed of iron carriers linked to antibiotic moieties. Albomycin was found to be active against bacteria that have a functional ferric hydroxamate transport system meaning that bacteria will actively transport albomycin until they die. We examined the activity spectrum of albomycin for bacterial pathogens and found that Enterobacteriaceae except species of Proteus and Morganella were sensitive. Resistance in the two genera was due to the lack of the ferric hydroxamate transport system. Among Gram-positive bacteria, Staphylococcus aureus and Streptococcus pneumoniae were highly sensitive, whereas Streptococcus agalactiae, Streptococcus pyogenes, and Staphylococcus epidermidis were resistant. The in vivo efficacy of albomycin was examined in mice infected with S. pneumoniae or Yersinia enterocolitica. A single dose of 10mg albomycin/kg body weight reduced the colony-forming units of Y. enterocolitica by three to four orders of magnitude. A single dose of 1mg albomycin/kg body weight was sufficient to clear S. pneumoniae infections in mice. In direct competition experiments with wild-type S. pneumoniae and its albomycin-resistant mutant, the recovery rate of the mutant was lower than for the wild-type indicating that the mutant had reduced fitness in the mouse model. We conclude that albomycin is effective in clearing infections caused by both Gram-positive and Gram-negative bacteria in a mouse model. Albomycin treatment reduces the bacterial load allowing the immune system to remove residual albomycin-resistant bacteria, and as such would make albomycin-based antibiotics an adjunct to treatment. The ferrichrome transport system serves as a Trojan horse to get albomycin into bacteria.

Yersinia septic shock following an autologous transfusion in a pediatric patient.

Although the literature on infections transmitted via transfused blood focuses on viruses, Yersinia enterocolitica can also cause severe infections in patients receiving transfusions. A 13-year-old patient developed severe sepsis after an autologous blood transfusion contaminated with Y. enterocolitica. The patient was an otherwise healthy female undergoing posterior spinal fusion for congenital scoliosis. Prior to surgery, the patient donated blood for perioperative and postoperative use. A few days before the donation, she had complained of abdominal pain and was experiencing mild diarrhea. The patient received four units of packed red blood cells (PRBCs) during the surgery. Intraoperatively, the patient developed fever up to 103.6 degrees F, became hypotensive requiring epinephrine and dopamine, and developed metabolic acidosis with serum bicarbonate concentration dropping to 16 mmol/l. The surgery team believed the patient was experiencing malignant hyperthermia and attempted to cool patient during the procedure. Postoperatively, the patient was transferred to the pediatric intensive care unit and treated for severe shock of unknown etiology. The patient further developed disseminated intravascular coagulation. The patient received supportive care and was started on ampicillin/sulbactam on postoperative day (POD) one which was changed to clindamycin, ciprofloxacin and tobramycin on POD two when blood cultures grew gram-negative bacilli. On POD three, cultures were identified as Y. enterocolitica and antibiotics were changed to tobramycin and cefotaxime based on susceptibility data. Sequelae of the shock included adult respiratory distress syndrome requiring intubation and a tracheostomy and multiple intracranial hemorrhagic infarcts with subsequent seizure disorder. Due to severe lower extremity ischemia, she required a bilateral below the knee amputation. The cultures of the snippets from the bags of blood transfused to the patient also grew Y. enterocolitica. This case illustrates the importance of considering transfusion related bacterial infections in patients receiving PRBCs. All patients in shock following any type of transfusion may require aggressive antibiotic therapy, until the diagnosis and etiology are known.

Comparison of the effects of deferiprone versus deferoxamine on growth and virulence of Yersinia enterocolitica.

Deferoxamine, a drug used to treat patients with iron overload, has the capacity to promote systemic Y. enterocolitica infections in humans. The aim of this study was to determine whether deferiprone, the only orally active alternative treatment, has the same potential. When Y. enterocolitica IP864 was grown in an iron-poor chemically defined medium, addition of deferoxamine promoted its growth, while various concentrations of deferiprone did not display this activity. Similarly, on iron-poor agar plates, various Y. enterocolitica strains were able to grow around paper disks impregnated with deferoxamine in a dose-dependent manner, while no growth was observed around the deferiprone disks. In a mouse experimental model of infection, the 50% lethal dose (LD(50)) of strain IP864 was decreased by more than 5 log units in mice pretreated with deferoxamine, while a deferiprone pretreatment did not affect it. Therefore, in contrast to deferoxamine, deferiprone does not enhance growth of pathogenic Y. enterocolitica in vitro and does not have the potential to promote Y. enterocolitica septicemia in a mouse model of infection. Deferiprone may thus represent a useful alternative iron-chelation therapy during invasive Y. enterocolitica infections.

Ciprofloxacin v placebo for treatment of Yersinia enterocolitica triggered reactive arthritis.

Patients with yersinia triggered reactive arthritis were double blind randomly allocated to receive treatment with ciprofloxacin 500 mg twice daily orally or placebo during three months. The diagnosis was made by serology (specific IgA and IgG antibodies to yersinia outer membrane proteins (yops)), positive culture, and/or demonstration of Yersinia enterocolitica antigen in colon biopsy specimens. Patients were evaluated monthly during and after treatment up to 12 months. Of 18 patients enrolled, all could be evaluated for safety, 16 for efficacy. There was a tendency towards faster remission and relief of pain in those receiving ciprofloxacin. Y enterocolitica was eliminated from the gut associated lymphoid tissue in six of seven patients receiving ciprofloxacin compared with none of nine patients receiving placebo. Patients receiving placebo had more and prolonged circulating IgA antibodies against yops than patients treated with ciprofloxacin.

No benefit of long-term ciprofloxacin treatment in patients with reactive arthritis and undifferentiated oligoarthritis: a three-month, multicenter, double-blind, randomized, placebo-controlled study.

OBJECTIVE: To investigate the effect of long-term antibiotic treatment in patients with reactive arthritis (ReA) and undifferentiated oligoarthritis. METHODS: One hundred twenty-six patients were treated with ciprofloxacin (500 mg twice a day) or placebo for 3 months, in a double-blind, randomized study. Of these patients, 104 (48 treated with ciprofloxacin and 56 treated with placebo) were valid for clinical evaluation: 55 were diagnosed as having ReA with a preceding symptomatic urogenic or enteric infection and 49 as having undifferentiated oligoarthritis. These 2 groups were randomized separately. The triggering bacterium was sought by serology and/or culture. The percentage of patients in remission after 3 months of treatment was chosen as the primary efficacy parameter. RESULTS: A triggering bacterium could be identified in 52 patients (50%): Chlamydia trachomatis in 13, Yersinia in 14, and Salmonella in 25. No patient was positive for Campylobacter jejuni or for Shigella. No difference in outcome was found between treatment with ciprofloxacin or placebo in the whole group or in subgroups of patients with ReA or undifferentiated oligoarthritis. No difference was seen in patients with a disease duration <3 months. Ciprofloxacin was not effective in Yersinia- or Salmonella-induced arthritis but seemed to be better than placebo in Chlamydia-induced arthritis. This difference was not significant, however, which might be due to the small sample size. CONCLUSION: Long-term treatment of ReA with ciprofloxacin is not effective; however, it might be useful in the subgroup of patients who have Chlamydia-induced arthritis. This has to be proven in a bigger study focusing on patients with Chlamydia-induced arthritis.

Comparison of ceftriaxone, amikacin, and ciprofloxacin in treatment of experimental Yersinia enterocolitica O9 infection in mice.

Ceftriaxone and ciprofloxacin were effective in the treatment of Yersinia enterocolitica O9 intestinal infection in mice. Amikacin was less effective. The impact of these drugs on indigenous bacteria from the intestinal microbiota was studied.

Experimental Yersinia-triggered reactive arthritis: effect of a 3-week course of ciprofloxacin.

Lewis rats were injected i.v. with live Yersinia enterocolitica, resulting in 1-2 weeks in an arthritis greatly resembling human reactive arthritis. Starting on day 3, 5, 10 or 13 after the bacterial inoculation, the rats were treated for 3 weeks with 20 mg/kg/day of ciprofloxacin. The development of arthritis was completely prevented if the antibiotic treatment was started on day 3. In a group of rats treated with ciprofloxacin from day 5 onwards, 2/14 rats already showed mild arthritis at the time when the treatment was started. Antibiotic treatment cured the arthritis of these rats as well as that of one additional individual in this group which developed arthritis. No later exacerbations occurred. If the antibiotic treatment was started on day 10 or 13, i.e. at the time of well-developed arthritis, no effect on arthritis was observed; rather, increased faecal excretion of Yersinia occurred following the antibiotic treatment. We conclude that experimental Yersinia reactive arthritis can be cured by antibiotics introduced at an early phase of arthritic development. Regarding acute human enterogenic arthritis, the decision on antibiotic treatment is not a straightforward matter. Our experimental results indicate that the earlier the treatment is started, the better the result, whereas late treatments seem to favour bacterial persistence.

Clinical features and antibiotic treatment of septic arthritis and osteomyelitis due to Yersinia enterocolitica.

Yersinia enterocolitica bone and joint infections are rare. Over a period of 7 months four patients with deep-seated skeletal infections due to Y. enterocolitica were seen at the University Hospital, Nottingham. Sites of infection included the knee (one patient) the hip (one) and the spine (two). None of the patients had major underlying disease or risk factors for developing invasive Y. enterocolitica infection. The organisms were sensitive to the second- and third-generation cephalosporins, gentamicin and fluoroquinolones. A literature search covering the period 1970-1994 revealed 20 other cases of skeletal infections due to Y. enterocolitica; there was no uniformity in the choice of antimicrobial agent for treating these infections. Oral ciprofloxacin was used as the principal antimicrobial agent in the patients described here and therapeutic success was achieved in three of these patients. Ciprofloxacin should be considered as first line therapy for invasive infections due to Y enterocolitica.

[The efficacy of using thymogen in an experimental infection caused by Yersinia enterocolitica]. / Effektivnost' primeneniia timogena pri éksperimental'noi infektsii, vyzvannoi Yersinia enterocolitica.

The effect of thymogen of the course of the infectious process caused by Y.enterocolitica serovars O3 and O9 in guinea pigs was studied. Thymogen was introduced into the animals on day 2 after their infection with Y.enterocolitica O3 and O9, introduced in daily injections of 10 micrograms/kg of body weight for 4 days. The evaluation of the characteristics of cell reactions in the lymphoid organs of the immune system (the thymus, the spleen, lymph nodes), nonspecific resistance and specific humoral response showed the effectiveness of using thymogen: this preparation produced an immunoregulatory effect in the infected animals; it decreased their polyclonal immune response, the development of autoimmune reactions and promoted the intensive development of delayed hypersensitivity (DH) after their enteral infection with Y.enterocolitica O9 and had no effect on the development of DH in the animals infected with Y.enterocolitica O3; it also enhanced the nonspecific resistance of the body, thus leading to a decrease in the dissemination of the infective agents in different organs and tissues and to their subsequent elimination from the body.

Effects of Yersinia enterocolitica infection on growth of the body and internal organs in newborn colostrum-deprived piglets.

Yersinia enterocolitica enteritis in newborn, colostrum-deprived piglets fed a human milk formula caused a reduced milk intake and decreased gain in weight but not length of the body. In infected piglets, the weight of the liver was less than in controls but other abdominal organs were unaffected. The weight of the caecum and small intestinal muscle were greater, but the length and weight of the small intestine and colon were not different. In infected piglets, the RNA concentration of the small intestinal mucosa was elevated whereas the concentrations of DNA and protein were unchanged, and total lactase activity was reduced. After antibiotic therapy, the liver weight was greater and the body weight increased at the same rate as the controls but was still lower at 14 days. The body weight of the control piglets increased linearly over the 14 days after birth. The stomach, pancreas and spleen grew more rapidly, but the liver more slowly, than the body as a whole but the kidneys had a minimum relative weight at 5 days. The total lactase activity and protein and RNA concentrations of the small intestinal mucosa decreased with age, the RNA to a greater extent than the protein.

Effect of antimicrobial treatment on chronic reactive arthritis.

In a double-blind study comprising 36 patients the effect of a three-month course of ciprofloxacin on chronic reactive arthritis was evaluated. At the end of the follow-up period 6 months after stopping the therapy, arthralgia, pain at movement and morning stiffness had decreased significantly compared to the values before the treatment in the ciprofloxacin group, whereas the Ritchie index and ESR showed a significant decrease in the control group. We conclude that further studies are necessary before the value of prolonged ciprofloxacin treatment of chronic reactive arthritis can be established.

Influence of antibiotics on IgA and IgG response and persistence of Yersinia enterocolitica in patients with Yersinia-associated spondylarthropathy.

The IgA and IgG antibody response to plasmid-encoded outer membrane proteins was studied in 59 patients with yersinia-associated spondylarthropathy during 15 months of follow-up. Initially, all patients had specific IgA and IgG antibodies to the 36 and 46 kDa and 30% also to the 26 and 58 kDa released proteins, which correlated with the finding of virulent Yersinia bacilli in intestinal biopsies. IgA disappeared in 69% of untreated patients after nine months and persisted in 31% after one year. IgA disappeared within three to six months in 81% of the patients treated with antibiotics for four to six weeks and persisted in 6% after one year (p less than 0.002). IgG antibodies to the 36 and 46 kDa outer membrane proteins persisted in 80% of all patients. Disappearance of IgA was coupled with disappearance of yersinia from intestinal biopsies.

Effect of the combination of clavulanic acid and cephalothin on an experimental infection with Yersinia enterocolitica in iron-overloaded mice.

Iron-overloaded mice were infected with a virulent strain of Yersinia enterocolitica by the oral route to study the effect of antimicrobial treatments. The effects of therapy were assessed by enumeration of viable yersiniae in Peyer's patches and in ileal contents. Combinations of cephalothin and clavulanic acid showed therapeutic effects, which were interpreted as in-vivo synergism, since each component alone was ineffective. Ceftazidime, which is relatively beta-lactamase resistant, showed in-vivo activity similar to that of the combination of cephalothin and clavulanic acid. These results suggest that clavulanic acid is able to protect cephalothin against Y. enterocolitica beta-lactamases in vivo, as has been shown previously in vitro.

Antibiotics in Yersinia enterocolitica infections.

A prospective study was undertaken to evaluate the incidence, course, effects of treatment and outcome of patients with Yersinia enterocolitica infections. A total of 189 patients were followed: 62.5% had enteric forms of illness, 20.6% extramesenteric forms, 23.2% arthritis and erythema nodosum. Lymphadenopathy with high fever and weight loss, a septic syndrome and hepatitis were predominant manifestations of the extramesenteric form. Ten per cent of the isolates (135) were susceptible to amoxycillin (4 mg/l), 38% to cephradine (8 mg/l), 82% to doxycycline (4 mg/l), 83% to chloramphenicol (4 mg/l), 85% to trimethoprim (1 mg/l), 87% to cefuroxime (8 mg/l), 92% to piperacillin (16 mg/l), 99% to gentamicin (1 mg/l) and 100% to cefotaxime (4 mg/l), pefloxacin (0.12 mg/l), ofloxacin (0.06 mg/l) and ciprofloxacin (0.016 mg/l). The majority of the patients with enteritis recovered without antibiotic therapy. The duration of enteritis was not significantly influenced by antibiotic treatment. Eighty five patients, 46 with enteric and 39 with extramesenteric forms were treated. The clinical response to co-trimoxazole was 71%, and to doxycycline 75%. Cefuroxime, ceftazidime, cefoperazone, piperacillin and gentamicin failed in seven of eight courses. Three patients treated with ciprofloxacin responded well. The role of quinolones in yersiniosis needs further attention.