Colisepticemia is the invasion of the bloodstream by coliform bacteria, primarily in neonates and immunocompromised animals. Affected animals show pronounced clinical signs of systemic disease and tend to deteriorate rapidly. A presumptive diagnosis is made on the basis of clinical signs in combination with hematologic and serum biochemical results. Blood cultures are considered a diagnostic gold standard; however, they lack sensitivity, and results are not immediately available.Treatment consists of immediate administration of antimicrobials along with fluid therapy and anti-inflammatories.
Septicemia caused by Escherichia coli is a sporadic disease recognized in most mammalian and avian species. E coli strains of intestinal or extraintestinal origin reach the bloodstream, where they cause systemic disease, and from there they can invade virtually every organ of the body.
Colisepticemia can present with clinical signs of acute septicemia or as a chronic or intermittent bacteremia with localization. Occurrence and severity of disease depend on the bacterial strain and its virulence, and, most importantly, on the presence of predisposing factors in the affected animal. Healthy animals with adequate immune function do not normally develop the disease, even if they are exposed to E coli. Accordingly, colisepticemia is not considered to be explicitly contagious.
Etiology and Epidemiology of Colisepticemia
Colisepticemia is caused by pathogenic strains of E coli that possess specific virulence factors, such as the capacity to adhere to and penetrate mucosal surfaces, effectively compete for iron in the extracellular space, or overcome the bactericidal plasma factors, allowing them to produce bacteremia and septicemia. Damage to the digestive tract mucosa caused by other bacterial, viral, or protozoal pathogens of the digestive tract greatly facilitates the translocation of E coli from the lumen of the intestinal tract into the body.
The single most important determinant of colisepticemia is an immunocompromised host. Severe and debilitating prior disease, possibly associated with damaged integrity of mucosal membranes of the digestive tract, or failure of transfer of passive immunity are common predisposing factors.
Colisepticemia most commonly occurs during the first weeks of life, with the highest incidence in animals 2–5 days old. However, it can also incidentally occur in older, immunocompromised individuals.
E coli is the most common pathogen isolated in blood from septic patients in most species. Approximately 30% of diarrheic calves with severe systemic clinical signs were found to be bacteremic or septicemic with E coli, which thus represents by far the most commonly isolated pathogen from blood cultures (1).
Transmission and Pathogenesis of Colisepticemia
It is assumed that the primary source of colisepticemia infection is the feces of infected animals, including healthy dams and neonates, and diarrheic neonate animals, which act as multipliers of the organisms. Invasion occurs through the mucosa of the digestive tract and possibly also the upper respiratory tract or via the umbilicus and the umbilical vein.
Septicemic strains of E coli produce endotoxin, which causes shock and rapid death. There is a period of subclinical bacteremia that, with virulent strains, is followed by rapid development of septicemia and death from endotoxemic shock.
A more prolonged course of colisepticemia, with localization of infection, polyarthritis, meningitis, and less commonly uveitis and nephritis, occurs with less virulent strains. Chronic disease also develops in calves that have acquired marginal concentrations of circulating immunoglobulin.
Initial E coli infection can be acquired from a contaminated environment. In groups of calves, transmission is by direct nose-to-nose contact, urinary and respiratory aerosols, or as the result of navel sucking or fecal-oral contact.
Clinical Findings of Colisepticemia
In peracute and acute colisepticemia, the clinical course is short (3–8 hours), and clinical signs are related to development of septic shock. Fever is not prominent, and the rectal temperature might even be subnormal. Lethargy and an early loss of interest in sucking are followed by depression, poor response to external stimuli, collapse, recumbency, cold extremities, and coma. Tachycardia, a weak pulse, and prolonged capillary refill time occur. The feces can become loose and mucoid, and profuse diarrhea can be present in complicated cases. Tremor, hyperesthesia, opisthotonos, and seizures occur occasionally; however, stupor and coma are more common.
As colisepticemia progresses, clinical signs specifically related to the failure of one or several organs, such as the lung, liver, kidney, or CNS, can become increasingly apparent. Death could occur as a result of either endotoxic shock or multiple-organ failure. Mortality approaches 100%.
With the more chronic form of colisepticemia, initial clinical signs are less severe, and the infection tends to localize to one or a few organ systems. Polyarthritis, omphalitis, omphalophlebitis, and meningitis can occur within the first week after the initial bacteremic phase.
In cases of arthritis caused by colisepticemia, affected joints show pain and increased fill, and the joint fluid has an increased inflammatory cell count and protein concentration. With meningitis, the CSF shows pleocytosis and an increased protein concentration; organisms might be evident on microscopic examination.
Less commonly, other bacteria, including other Enterobacteriaceae, Streptococcus spp, and Pasteurella spp, produce septicemic disease in young calves. The clinical signs are similar; however, it can be differentiated by culture. As with colisepticemia, the primary determinant of these infections is impaired function of the immune system.
Diagnosis of Colisepticemia
Presumptive: clinical evaluation, hematologic and serum biochemical testing
Definitive: blood culture
Bacterial culture of blood obtained aseptically is considered the gold standard to confirm the diagnosis of septicemia by E coli. Although a positive culture result confirms the diagnosis, positive culture results may sometimes be obtained post mortem, even when blood cultures obtained from the living patient were negative. Another limitation of the use of blood cultures in acutely sick patients is the lag time of at least two days before results are available.
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A tentative diagnosis of colisepticemia can be made on the basis of clinical presentation with the support of available laboratory tests. Although there is no single serum biochemical or hematologic parameter that unambiguously confirms the diagnosis, interpreting the available evidence is the common approach to determining the likelihood that the patient has developed septicemia. Scoring systems using a combination of clinical, hematologic, and serum biochemical parameters have been proposed for this purpose.
Clinical parameters considered most reliable in assessing the risk of septicemia include the severity of altered demeanor and disturbed cardiovascular and respiratory function. Simultaneous dysfunction of multiple organ systems is also considered highly suggestive of septicemia.
Marked leukopenia is common in the early stage of severe cases of colisepticemia. A degenerative left shift of neutrophils and evidence of toxicosis of neutrophils, as well as pronounced hypoglycemia and sometimes lactatemia, can develop later. Increased blood lactate concentrations are thought to be a sign of disturbed oxygen and glucose utilization as well as of impaired tissue perfusion and beginning organ function disturbances. Hypoproteinemia in serum or plasma is the result of increased globulin consumption; however, it is also suggestive of the development of vascular leakage.
Because failure of transfer of passive immunity is common in neonates, subnormal serum IgG and total protein concentrations cannot be solely attributed to sepsis in these patients. Subnormal platelet counts are the result of a consumptive coagulopathy, and so-called acute phase proteins, such as serum amyloid A, C-reactive protein, or haptoglobin in serum or plasma, have been proposed as diagnostic parameters to support the diagnosis of septicemia. These parameters, however, have not yet been established for this purpose in cattle.
Treatment of Colisepticemia
Immediate: administration of IV antimicrobials
Supportive care: anti-inflammatories and IV fluids
Treatment for colisepticemia requires immediate administration of IV antimicrobials. This initial treatment should be accompanied by supportive IV fluid therapy. The use of anti-inflammatories in patients with suspected septicemia is common practice; however, it is primarily made on the basis of empirical evidence.
Following the guidelines of prudent antimicrobial use, antimicrobial therapy for colisepticemia should be determined on the basis of the results of culture and susceptibility testing whenever possible. Suspected septicemia, however, is a medical emergency requiring immediate initiation of vigorous antimicrobial therapy. Because there is no time for susceptibility testing, the initial antimicrobial choice should be a bactericidal drug that has a high probability of efficacy against gram-negative organisms.
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In the absence of susceptibility test results, the choice of antimicrobial drug to use for colisepticemia is at the discretion of the attending veterinarian and can be made on the basis of personal experience with treatment of similar cases or on test results of earlier cases from the same herd. The use of veterinary critically important antimicrobials, such as third- or fourth-generation quinolones or cephalosporins, as a first choice is discouraged because of the potential for development of antimicrobial resistance. However, such choices can be justified if, for example, earlier cases on the same farm identified multiresistant strains of E coli.
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In the absence of susceptibility test results and without indications for a resistance against amoxicillin, a recommended off-label treatment protocol consists of administering amoxicillin trihydrate at a loading dose of 20 mg/kg, IV, followed by 10 mg/kg, IM, every 12 hours for 10 days (2).
IV administration of large volumes of balanced electrolyte solution over several hours is essential to correct hypovolemia and assure adequate peripheral tissue perfusion in patients with colisepticemia. With suspected septicemia, however, the infusion rate should not exceed 20 mL/kg/h to prevent cerebral edema that might result from increased capillary permeability in combination with decreased oncotic pressure in blood.
IV fluids used in the treatment of colisepticemia should include dextrose in amounts adequate to correcthypoglycemia, which can be challenging to control in cases of acute sepsis because of the massive energy uptake of activated immune cells. It is advisable to monitor the blood glucose concentration — for example, with a handheld glucometer — to adjust the fluid rate to maintain euglycemia.
NSAIDs are often recommended on empirical grounds or by expert opinion; however, unequivocal evidence to support the use of these drugs in septic patients is lacking. The primary benefit of using anti-inflammatory drugs appears to be pain mitigation and antipyrexia. Clinical studies conducted in humans and various animal species have failed to consistently identify an improved treatment outcome (3, 4). Glucocorticoids have also been proposed to treat septicemia, again without convincing supporting scientific evidence.
Control and Prevention of Colisepticemia
Calves that acquire adequate concentrations of immunoglobulin from colostrum are resistant to colisepticemia. Therefore, prevention depends primarily on management practices that ensure an adequate and early intake of colostrum. The adequacy of the farm’s practice of feeding colostrum should be monitored, and corrective strategies can be applied as required.
Natural sucking does not guarantee adequate concentrations of circulating immunoglobulins, and calves should be fed 3–4 L of first-milking colostrum containing a minimal total mass of 150 g of IgG, using a nipple bottle or an esophageal feeder, within 2 hours after birth, followed by a second feeding at 12 hours (5).
A cow-side immunoassay test or testing colostrum with a Brix refractometer or colostrometer can assist in selection of colostrum with adequate immunoglobulin concentration. Although the circulating concentration of immunoglobulin required to protect against colisepticemia is low, high concentrations are desirable to decrease susceptibility to other neonatal infectious diseases. Cutoff values for IgG concentration in plasma of neonate calves in the first days of life have been categorized as excellent (> 25 g/L), good (18–24.9 g/L), fair (10–17.9 g/L), or poor (< 10 g/L) (6).
When natural colostrum is not available for a neonate calf, commercial colostrum substitutes containing 25 g of IgG will provide immunoglobulin to improve protection against colisepticemia if fed early in the absorptive period. Small-volume hyperimmune serum is of benefit only when it contains antibodies specifically against the particular bacterial serotype associated with an outbreak.
The risk of early infection should be minimized by hygiene in the calving area.
Key Points
Colisepticemia is a sporadic disease primarily affecting neonates and immunocompromised animals.
The occurrence and severity of disease depends on the virulence of the causative bacterial strain and, most importantly, the predisposition to disease of the affected individual.
Affected animals show clinical signs of severe systemic disease and tend to deteriorate rapidly.
Effective treatment requires rapid, thorough antimicrobial, anti-inflammatory, and fluid therapy.
For More Information
Pas M, Bokma J, Lowie T, Boyen F, Pardon B. Sepsis and survival in critically ill calves: Risk factors and antimicrobial use. J Vet Intern Med. 2023;37(1):374-389.
Pas M, Bokma J, Boyen F, Pardon B. Clinical and laboratory predictors for bacteremia in critically ill calves. J Vet Intern Med. 2024;38(6):3367-3383.
References
Lofstedt J, Dohoo IR, Duizer G. Model to predict septicemia in diarrheic calves. J Vet Intern Med. 1999;13(2), 81-88. doi:10.1892/0891-6640(1999)013%3C0081:mtpsid%3E2.3.co;2.
House JK, Izzo MM, Page SW, Browning GF, Norris JM. Antimicrobial prescribing guidelines for dairy cattle. Aust Vet J. 2024;102(4). doi:10.1111/avj.13311.
Freeman, B. D., & Natanson, C. (2000). Anti-inflammatory therapies in sepsis and septic shock. Expert Opin Investig Drugs. 2000;9(7), 1651-1663. doi:10.1517/13543784.9.7.1651.
Venkatesh B, Cohen J. Why the adjunctive corticosteroid treatment in critically Ill patients with septic shock (ADRENAL) trial did not show a difference in mortality. Crit Care Med. 2019;47(12), 1785-1788. doi:10.1097/ccm.0000000000003834.
Godden SM, Lombard JE, Woolums AR. Colostrum management for dairy calves. Vet Clin North Am Food Anim Pract. 2019;35(3), 535. doi:10.1016/j.cvfa.2019.07.005.
Lombard J, Urie N, Garry F, Godden S, et al. Consensus recommendations on calf-and herd-level passive immunity in dairy calves in the United States. J Dairy Sci. 2020;103(8), 7611-7624. doi:10.3168/jds.2019-17955.
