Fibrin deposits and organ failure in newborn foals with severe septicemia

Background: Septicemia in human neonates frequently is complicated by activation of the coagulation system, disseminated intravascular coagulation (DIC) and multiple organ failure syndrome, which may contribute to high mortality. In adult horses with DIC, the lung has been the organ most frequently affected by fibrin deposits. In addition, in vivo studies suggest that hemostatic mechanisms may be immature in foals <1‐day old. Hypothesis: Newborn foals with severe septicemia have fibrin deposits in their tissues independently of their age, and these fibrin deposits are associated with organ failure. Animals: Thirty‐two septic and 4 nonseptic newborn foals euthanized for poor prognosis. Methods: Tissue samples (kidney, lung, and liver) collected on postmortem examination were stained with phosphotungstic acid hematoxylin (PTAH) and immunohistochemistry (IHC) for blind histologic examination. A fibrin score (grades 0–4) was established for each tissue sample and for each foal. Medical records were reviewed for assessing clinical evidence of organ failure during hospitalization. Results: Fibrin deposits were found in most septic foals (28/32 when using IHC and 21/32 when using PTAH), independently of the age of the foal. The lung was the most affected tissue (97% of the septic foals). Additionally, organ failure was diagnosed in 18/32 septic foals (8 with respiratory failure, 14 with renal failure), although a statistical association with severe fibrin deposition was not identified. Conclusions and Clinical Importance: Nonsurviving septic foals have fibrin deposits in their tissues, a finding consistent with capillary microthrombosis and DIC.     

Disposition of oral clarithromycin in foals

Clarithromycin offers numerous advantages over erythromycin and thus, is an attractive alternative for the treatment of Rhodococcus equi infections in foals. The disposition of clarithromycin was investigated in 6 foals after intragastric administration at a dose of 10 mg/kg body weight. Detectable serum concentrations of clarithromycin were found in 3 of 6 foals at 10 minutes and in all foals by 20 minutes post-administration. Time to peak serum concentration (Tmax) was 1.5 hours and peak serum concentration (Cmax) was 0.92+/-0.17 microg/ml. Mean serum concentrations decreased to 0.03 microg/ml at 24 h. No adverse reactions were noted during or after IG administration in any of the foals. Based on the pharmacokinetic parameters, the MIC90 of R. equi isolates, and predicted steady state concentrations, an oral dose of 7.5 mg/kg given every 12 hours would appear appropriate for the treatment of R. equi infections in foals.     

Antimicrobial-induced endotoxin and cytokine activity in an in vitro model of septicemia in foals

OBJECTIVE: To determine which antimicrobials that are used to treat neonatal foals with septicemia attributable to Escherichia coli will minimize endotoxin release from bacteria and subsequent activity of inflammatory mediators while maintaining bactericidal efficacy. SAMPLE POPULATION: Blood samples from 10 healthy foals. PROCEDURE: Escherichia coli isolates A and B were isolated from 2 septicemic foals, and minimal inhibitory concentrations (MIC) were determined for 9 antimicrobials. Five of these antimicrobials were tested in vitro at 2 and 20 times their respective MIC. Whole blood or mononuclear cells grown in tissue-culture media were incubated with 105 colony-forming units of E. coli and each antimicrobial or saline (0.9% NaCl) solution. After 6 hours, number of viable bacteria remaining was determined, and supernatant was tested for endotoxin and tumor necrosis activity. RESULTS: Testing in whole blood was compromised by bactericidal effects of the blood itself. In mononuclear cell suspensions, each antimicrobial significantly reduced the number of viable bacteria to low or undetectable amounts. Antimicrobials did not differ significantly in efficacy of bacterial killing. Amikacin used alone or in combination with ampicillin resulted in significantly less endotoxin activity than did ampicillin, imipenem, or ceftiofur alone. There was a correlation between TNF-alpha and endotoxin activity. CONCLUSIONS AND CLINICAL RELEVANCE: Aminoglycosides appear less likely to induce endotoxemia and TNF-alpha synthesis during bactericidal treatment of E. coli septicemia, compared with beta-lactam antimicrobials. Use of ampicillin, imipenem, or ceftiofur in the treatment of septicemic neonatal foals should be accompanied by appropriate treatment for endotoxemia.     

Concentrations of amino acids in the plasma of neonatal foals with septicemia

Concentrations of amino acids in the plasma of 13 neonatal foals with septicemia were compared with the concentrations of amino acids in the plasma of 13 age-matched neonatal foals without septicemia. Analysis of the results revealed significantly lower concentrations of arginine, citrulline, isoleucine, proline, threonine, and valine in the plasma of foals with septicemia. The ratio of the plasma concentrations of the branched chain amino acids (isoleucine, leucine, and valine) to the aromatic amino acids (phenylalanine and tyrosine), was also significantly lower in the foals with septicemia. In addition, the concentrations of alanine, glycine, and phenylalanine were significantly higher in the plasma of foals with septicemia. Therefore, neonatal foals with septicemia had significant differences in the concentrations of several amino acids in their plasma, compared with concentrations from healthy foals. These differences were compatible with protein calorie inadequacy and may be related to an alteration in the intake, production, use, or clearance of amino acids from the plasma pool in sepsis.     

Tumor necrosis factor activity in serum from neonatal foals with presumed septicemia.

A study was performed to determine prevalence of tumor necrosis factor (TNF) activity in serum of equine neonates with presumed sepsis and to determine correlation between serum TNF activity and severity and outcome of disease. Twenty foals less than 21 days old were considered suitable for inclusion in this study by satisfying clinical and laboratory criteria suggestive of septicemia. At admission, blood samples were collected from all foals for determination of serum TNF activity, then clinical course and outcome of disease were recorded. Thirty-one clinically normal foals less than 21 days old served as controls for serum TNF activity. Serum TNF activity was estimated by use of an in vitro cytotoxicity bioassay and WEHI 164 clone-13 murine fibrosarcoma cells. Of the 20 foals with presumed sepsis, 5 had high serum TNF activity. Mean heart rate (P less than 0.005), mucosal petechial hemorrhages (P = 0.06), and death rate (P = 0.06) were greater in the group of foals with high serum TNF activity. These foals also had a lower mean neutrophil count (P less than 0.001), greater band-to-segmented neutrophil ratio (P less than 0.0001), and more prevalent neutrophil toxic changes (P = 0.07) than did foals without serum TNF activity (P = 0.02). Joint swelling was more prevalent in foals without serum TNF activity. Results of the study indicate that serum TNF activity is correlated with clinical criteria of sepsis in equine neonates. An association was apparent between disease severity and serum TNF activity in this group of foals with presumed septicemia.     

Anaerobic bacterial pneumonia with septicemia in two racehorses

Anaerobic bacterial pneumonia with septicemia was diagnosed in 2 Thoroughbred racehorses referred with respiratory tract disease that had failed to respond to initial treatment with various antibiotics including penicillin and trimethoprim-sulfamethoxazole. Multiple anaerobic organisms, including Bacteroides spp and Fusobacterium spp, were isolated from blood and transtracheal aspirates obtained from both horses and from aspirates of cutaneous nodules obtained from 1 horse. The latter horse responded to metronidazole treatment followed by procaine penicillin G administration and regained its health over the following 6 months. The other horse did not respond as favorably to a similar antibiotic regimen and died following an acute episode of pulmonary hemorrhage after remaining intermittently febrile for 7 weeks. Although in vitro antimicrobial susceptibility tests indicated that all anaerobic organisms isolated from both horses were susceptible to penicillin, the infection in these horses responded poorly to initial treatments with this drug. We speculated that adequate penicillin concentration was not attained in the deep foci of infection in the lungs. Animals with anaerobic bacterial infections that fail to respond to penicillin or from which penicillin-resistant anaerobes are isolated may benefit from treatment with metronidazole.     

Protection of foals against experimental Rhodococcus equi pneumonia by oral immunization.

Two groups of three one to three week old foals were immunized orally on four occasions over five weeks with two strains of Rhodococcus equi, a clinical isolate from a pneumonic foal and a laboratory passaged Congo red negative variant of this strain. Three nonimmunized foals of similar age acted as controls. Three weeks after the last immunization, all foals were challenged on five occasions over seven days by aerosol infection with about 10(10) of the pneumonic foal isolate on each occasion. Control foals became seriously ill and were euthanized. Immunization with either strain protected foals equally against the challenge, and resulted in rapid lung clearance. Oral immunization can thus protect foals against severe challenge with R. equi. The proteins associated with Congo red colony staining appear not to be involved in protective immunity.     

The effect of oral ivermectin on immature ascarids in foals

Orally administered ivermectin^awas 100% effective against experimentally induced 11-day-old infections of Parascaris equorum (L₃) in 2 trials. In 4 additional trials there was 98% efficacy of ivermectin treatment against induced 28-day-old infections of P. equorum (L₄). In 2 trials with natural infections of ascarids, invermectin paste had 93% efficacy against immature P. equorum and 100% efficacy against the adult. One of the latter 2 trials also emphasized the potential problem of reinfection.     

Pharmacokinetics of rifampin given as a single oral dose in foals

Six foals from 6 to 8 weeks of age were given a single oral dose of rifampin at a dosage of 10 mg/kg of body weight. Serum rifampin concentrations were measured serially during a 24-hour period. The mean peak serum rifampin concentration was 6.7 micrograms/ml at 4 hours after treatment. The concentration decreased slowly, and at 24 hours the mean value was 2.7 micrograms/ml. The elimination half-life was 17.5 hours, and the elimination rate constant was 0.04/hr.     

Disseminated candidiasis secondary to fungal and bacterial peritonitis in a young dog

Objective – To describe a severe case of bacterial sepsis and disseminated candidiasis in a previously healthy dog.
Case Summary – Fungal sepsis was identified in a 2-year-old dog following intestinal dehiscence 4 days after abdominal surgery. Septic peritonitis was identified at admission and evidence of dehiscence at the previous enterotomy site was found during an exploratory laparotomy. Both gram-positive cocci and Candida albicans were cultured from the abdominal cavity. Candida sp. was also subsequently cultured from a central venous catheter. Euthanasia was performed due to failure to respond to therapy. Fungal organisms, morphologically consistent with Candida spp., were found in the lungs and kidney on postmortem histopathologic examination indicating disseminated candidiasis.
New or Unique Information Provided – Candida peritonitis is a well-recognized entity in humans and contributes to morbidity and mortality in critically ill patients. Abdominal surgery, intestinal perforation, presence of central venous catheters, and administration of broad-spectrum antibiotics are all considered to be suspected risk factors. This report describes the first known case of systemic candidiasis occurring secondary to Candida peritonitis and bacterial sepsis in a critically ill dog.     

Pharmacokinetics of oral doxycycline and concentrations in body fluids and bronchoalveolar cells of foals

The objective of this study was to determine the disposition of orally administered doxycycline in foals. Six healthy 4- to 8-week-old foals were used. Doxycycline was administered to each foal via the intragastric (IG) route at dosages of 10 and 20 mg/kg, in a cross-over design. After the first 10 mg/kg dose, five additional doses were administered at 12-h intervals. A microbiological assay was used to measure doxycycline activity in serum, urine, peritoneal fluid, synovial fluid, cerebrospinal (CSF), pulmonary epithelial lining fluid (PELF), and bronchoalveolar (BAL) cells. Following administration at 10 mg/kg, mean+/-SD time to peak serum doxycycline activity (tmax) was 3.0+/-1.2 h, maximum serum activity (Cmax) was 2.54+/-0.27 microg/mL, and terminal half-life (t1/2) was 8.5+/-2.8 h. Administration at a dose of 20 mg/kg resulted in a significantly longer tmax (5.5+/-1.8 h) as well as a tendency toward higher Cmax (2.89+/-0.33 microg/mL) and longer t1/2 (11.9+/-2.6 h). After multiple IG doses, doxycycline activity in CSF was significantly lower than concurrent serum activity, whereas peritoneal fluid, synovial fluid, and BAL cell doxycycline activity was similar to concurrent serum activity. Doxycycline activity in urine and PELF was significantly higher than that found at other sites. Oral administration at a dosage of 10 mg/kg every 12 h would maintain serum, PELF, and BAL cell activity above the minimum inhibitory concentrations of Rhodococcus equi, beta-hemolytic streptococci, and other susceptible bacterial pathogens for the entire dosing interval.