EQUINE VETERINARY JOURNAL
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Equine vet. J . (1992) 24 ( 5 ) 407-410
Bacteraemia and pneumonia in a neonatal foal caused by Streptococcus pneumoniae J. C. MEYER, ANNE KOTERBA, G. LESTER and B. L. PURICH
Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida 326 10, USA.
Introduction STREPTOCOCCUS pneumoniue type 3 has been isolated from a tracheobronchial aspirate of a 6-month-old foal with pneumonia but other potentially pathogenic bacteria were cultured from the aspirate (Benson and Sweeney 1984). Isolation of S. pneumoniae from a 33-day-old foal with septic arthritis, pleuropneumonia, pericarditis and septicaemia has been reported, but the serotype of the isolate was not determined (Harms 1941). S . pneumoniue has been isolated from the respiratory tract of adult horses. A causal relationship between such isolates and respiratory disease has not been established (Benson and Sweeney 1984; Burrell, Mackintosh and Taylor 1986). Pneumococcal infections in man are most common in children and the aged. The predominant forms of such infections are pneumonia and meningitis often accompanied by bacteraemia and septicaemia. Factors that predispose to pneumococcal infection in adults include alcoholism, head injuries, and splenectomy. Pneumococcal infections in infants are sporadic, and associated with a high mortality rate (Guzzardo, Hacker and Walker 1988). Group B streptococcal infection is a more common cause of fulminating pneumonia and septicaemia amongst infants. This paper reports the clinical course of overwhelming pneumonia and bacteraemia caused by Streptococcus pneumoniae type 3 in a new born foal and efforts to identify the source of the infection.
Case history
weight was estimated at 5-7%. The mucous membranes were dark pink, capillary refill time was less than 2 sec, the quality of the pulse was good. Body temperature was 39.3"C, the heart rate 70-80 beats/min, and the respiratory rate 80-90 breathshin. The nostrils were flared, and there was a marked abdominal component to the breathing pattern. Thoracic auscultation revealed wheezes and crackles bilaterally, more pronounced over the ventral lung fields. Bilateral entropion and corneal ulceration were also noted.
Clinical pathology Because of the marked respiratory distress, the foal was immediately placed on nasal oxygen insufflation at 8 litres/min. Arterial blood gas analysis on supplemental oxygen revealed severe respiratory acidosis, mild metabolic acidosis, and hypoxaemia (Table I). The serum IgG concentration was > 800 mg/dl (CITE, IDEXX, Inc., Portland, ME, USA). The total white blood cell count was 1.2 x logflitre, with severe neutropenia (0.1 x lOg/litre), lymphopenia (0.74 x logflitre), and a degenerative left shift (0.19 x l09/litre bands, 0.070 x lo9 metamyelocytes/litre) with toxic changes. The PCV was 0.42 litresflitre, RBC count was 9.95 x IO**/litre, total plasma protein concentration 54 gflitre, and plasma fibrinogen concentration 5 ghitre. Reagent strip analysis of whole blood (Chemstrips, Boehringer Mannheim Diagnostics, Indianapolis, IN, USA) indicated hypoglycaemia (2.2 mmol/l). Serum electrolytes, BUN, and creatinine concentrations were within normal limits with the exception of those of sodium (129 mmol/litre), chloride (93 mmolflitre) and calcium (2.0 mmol/litre), which were low. Blood was withdrawn aseptically and cultured aerobically and anaerobically in Brucellu and Columbu blood culture broth. The broths were incubated at 37°C. Within 24 h, the aerobic culture
A 55-h-old, Thoroughbred colt of 335 days' gestational age was referred to the University of Florida Veterinary Medical Teaching Hospital (VMTH) with weakness of sudden onset and respiratory distress. The dam had been shipped to the breeding farm late in gestation and this was her first foal. The birth was attended, and the delivery process and fetal membranes were judged to be within normal limits. The foal stood and sucked within 2 h of birth, passed normal-looking meconium and behaved normally during the first 48 h of life. On the morning of the 3rd post-natal day the foal was found recumbent, dehydrated, and breathing rapidly. It was immediately shipped to the Veterinary Medical Teaching Hospital (VMTH).
TABLE 1: Blood values for the Infected foal
Physical examination
PH
On arrival at the VMTH the foal was weak and unable to stand without assistance. Body weight was 54 kg, and its nutritional state appeared adequate. Dehydration as a percentage of body
Procedure
Day 1 1O:OO h Supplemental 02
7.105
1 3 x 0 2 (mmHg) 74.5
Paop(mmHg) 40 HCO3- (mEqll) 23.6 BE (mEq/l) -7.0
Day 1 Day 1 Day2 1500 h 1O:OO h 10:43 h Manual Intermittent off ventilation mandatory ventilator with Ambu bag ventilation (03:OO h) 7.182 63.0 45 23.8 -5.1
7.385 41 .O 108 24.9 0.4
7.104 65.0 54.2 24.0
-5.2
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Fig I : Thoracic radiograph taken in lateral recumbency shortly after admission. There is a severe interstitial and alveolar pattern within the l ~ n and g vety little air present
Fig 2 : Luteral thoracic radiograph r,f' the fiml taken on Day 4 in hospital. The severity ofthe pulmonary infiltrate hus increased
was positive for S. pneumoniue. The organism appeared encapsulated, moist, mucoid, and transparent with colonies that tended to run together. Further identification was based on the Gram stain, alpha haemolysis, catalase reaction and optochin sensitivity. A subsequent culture of purulent material draining from an endotracheal tube was plated on Columbia agar with 5% sheep blood, Mackonkey agar, colistin/nalidixic acid agar with 5% sheep blood was incubated at 37°C in an atmosphere of air enriched with 5% C02. This culture also yielded a pure growth of S. pneumoniue with the same susceptibility pattern (ie susceptible to penicillin, ampicillin, cephalothin, erythromycin, co-trimoxazole, tetracycline, and ceftazidime but resistant to gentamycin as determined by the Kirby-Bauer method). both isolates were sent to The Center for Disease Control (Atlanta, Georgia, USA) for serotyping and were found to be of serotype 3. Based on these results the foal was treated with potassium penicillin G and ceftazidime. Chest radiography taken in lateral recumbency revealed a severe, diffuse interstitial and alveolar pattern throughout the lung fields (Fig I). The pattern appeared more pronounced in the antero-ventral view. These findings were consistent with a severe bacterial pneumonia.
became partly occluded with a copious purulent exudate, necessitating frequent clearing of the airway by suction. Over the first 24 h in hospital, the foal became much stronger and considerably less co-operative. Phenobarbital at a loading dose of 20 mg/kg iv was ineffective in adequately sedating the foal. Doses of xylazine, butorphanol and finally detomidine were administered frequently in an attempt to prevent struggling and accidental extubation. In spite of the use of these agents, it became increasingly difficult to maintain the foal on the ventilator. Periodic episodes of violent struggling resulted in fever spikes to over 40.2'C. These were controlled with alcohol, cold water baths and flunixin meglumine. After 26 h of mechanical ventilation, an attempt was made to remove the foal from the ventilator. Within 3 h severe respiratory acidosis and hypoxaemia recurred (Table I). The foal was therefore re-intubated and mechanical ventilation resumed. Peak inspiratory pressures at the same ventilator settings were 5 M cmH20. After being mechanically ventilated for another 20 h the foal was again disconnected from the ventilator. During the brief periods off the ventilator the foal was allowed to suck from a bottle. This provided inadequate nutritional support and consideration was given to beginning total parenteral nutrition. After the foal had been in hospital for 6 h, furosemide (50 mg, twice/day) was instituted to combat pulmonary oedema. In addition, after 24 h in hospital the foal received aminophylline (250 mg, 3 times/day). The furosemide therapy was discontinued after 48 h and the aminophylline therapy continued for the duration of the foal's stay. By 72 h after admission, the foal's WBC count had increased to 11.2 x IOgAitre, and plasma fibrinogen concentration had remained at 500 mg/dl, but his respiratory function appeared to be deteriorating further. He could not tolerate even brief periods without mechanical ventilation, and appeared to be weakening. When repeated chest radiographs revealed that the pulmonary infiltrates were worsening (Fig 2). permission was obtained for the foal to be destroyed.
Case management
Immediately after arterial blood gas results were obtained, a nasotracheal tube was passed, and the foal was manually ventilated by means of a I-litre AMBU bag supplied with supplemental oxygen. A balanced electrolyte solution and 5% (w/v) dextrose solution (Plasmalyte 148 with 5% dextrose, Baxter Healthcare Corp.) was infused as a continuous drip, and a broad-spectrum antibiotic regimen was instituted. Amikacin (7 mg/kg, 3 times/day), ampicillin (20 mg/kg, 4 times/day) and ceftazidime (20 mg/kg, 3 times/day) were administered pending bacteriological results. Manual ventilation only partly corrected the respiratory acidosis (Table I). Although the owner was given a very poor prognosis for the foal's survival, he requested that treatment be attempted. Intermittent mandatory ventilation was instituted by means of an Emerson volume-cycled ventilator. Machine settings of 12- 16 breathshin. tidal volume of 800 ml,as measured at the proximal endotracheal tube with a respirator, positive end - expiratory pressure (PEEP) of 5 cmH20, and fractional inspired oxygen (no2)of 0.8 generated a peak inspiratory pressure (PIP) of 40-60 cm H20 and maintained arterial blood gases within the normal range (Table I). Over the next 12 h, the FIO2 steadily decreased from 0.8 to 0.5, as Pao2 improved. The endotracheal tube often
Pathology
Grossly, the lungs were firm, mottled-red, and heavy. Microscopically, the cellular infiltrate in the interstitium comprised macrophages and hyperplastic type I1 pneumocytes. There were numerous alveoli and terminal bronchioles containing a deeply staining basophilic material. The morphological diagnosis was a severe, diffuse, subacute, interstitial pneumonia with associated intra-alveolar material. The intra-alveolar material
EQUINE VETERINARY JOURNAL
was thought to be milk or inhaled amniotic squamous cells. A Gram stain identified Gram-positive cocci associated with several vessels around alveoli. Cultures of lung, heart, blood and bone marrow did not yield any bacterial growth.
Epidemiology An attempt was made to determine the source of the infection. The uterus and nasopharyngeal region of the dam were swabbed 5 days post parturn. The uterine swab was negative for the organism, but the nasopharyngeal swab yielded a pure culture of S . pneumoniae type 3 (also serotyped at the Center for Disease Control, Atlanta, Georgia). The mare was treated with penicillin G (20,000 iu/kg, timedday) for 5 consecutive days. A nasopharyngeal swab obtained after the dose did not yield S. pneumoniae. Nasopharyngeal swabs were collected from 8 brood mares that had been in contact with the dam at the farm shortly before or after foaling. In addition, nasopharyngeal swabs were taken from 6 racehorses in training at the farm but which had no contact with the affected foal's dam. All 14 of these cultures were negative for S. pneumoniae. Three people had been in contact with the mare and foal; they were the farm manager, his son and an assistant. Before the foal's birth the assistant was being treated with antibiotics for an undiagnosed respiratory infection. Concurrent with the foal's illness the farm manager's son developed a cough and became febrile, requiring antibiotic therapy. The farm manager also developed a mild throat irritation. Sputum and throat cultures taken from the assistant and the farm manager's son after the antimicrobial therapy were negative.
Discussion S. pneumoniae is an alpha-haemolytic, Gram positive, lanceolate
coccus seen in pairs. Short chains of cocci are most commonly associated with serotype 3. There are 83 serotypes of S. pneumoniae which are capsular polysaccharides. The pneumococci are highly susceptible to physical agents such as heat and drying. Most strains of S. pneumoniae demonstrate striking susceptibility to penicillin G and erythromycin with rate clinical isolates being resistant. The mechanism of resistance to penicillin by some serotypes of S. pneumoniae is unknown, but it is not due to elaboration of betalactamase or R plasmids (Hoeprich and Jordan 1989). S. pneurnoniae is often found as a normal inhabitant of the upper respiratory tact of humans and it may be isolated from up to 60% of normal people (Austrian 1986). The rate of colonization varies with season, age and density of population (Gray, Tumer and Dillon 1982). S . pneumoniae is the most common cause of community-acquired pneumonia in humans. Classical pneumococcal pneumonia in the adult strikes suddenly. The victim develops a shaking chill which leads to a sustained fever. A productive cough producing rusty mucopurulent sputum develops. The patient often develops pleuritis and pulmonary consolidation. The disease is noted for its dramatic and sudden onset. The prognosis for recovery in adults with antimicrobial therapy is good provided there is no underlying disease which adversely affects pulmonary defence mechanisms (Hoeprich and Jordan 1989). By contrast, the disease in children is sporadic and associated with a high mortality rate (Guzzardo et a1 1988). S . pneurnoniae accounts for only 5 % of the cases of neonatal bacteraemia. The foal in this report had a severe, acute bronchopneumonia and severe respiratory distress. The radiographic changes in this case were suggestive of either severe bacterial pneumonia or hyaline membrane disease (HMD) (Koterba, Drummond and Kosch 1990). However, HMD was considered unlikely because the foal was born at term, and signs of respiratory distress did not appear until Day 3 of age. Culturing the blood and tracheal secretions was useful in reaching a specific diagnosis. Recent reports focus on the isolation of S. pneurnoniae from
409
the upper respiratory tract of adult horses and do not provide direct evidence to implicate the isolation of this organism with disease (Benson and Sweeney 1984; Burrell et al 1986). There appears to be an asymptomatic carrier state in horses (Burrell et al 1986). However, the low incidence of recovery of S. pneumoniae from horses compared with humans suggests that the horse acquires the microbe from humans rather than acting as a reservoir for human infection (Benson and Sweeney 1984). One perplexing question in this case is why the foal acquired this particular type of infection. This was the first time that S. pneumoniae had been isolated from a neonatal foal admitted to our hospital. We considered that an infection acquired in utero was unlikely. The foal was born at term and appeared of normal size, the placenta appeared grossly normal, and the foal appeared clinically normal until Day 3 of life. The foal also seemed at low risk of becoming infected post parturn. There were no problems noted at birth, the foal had a normal serum concentration of IgG at 24 h of age, and he appeared vigorous and strong. However, on the basis of clinical signs and the history, it is most likely that he did acquire the infection following birth. The fact that the foal appeared to have an adequate amount of IgG and yet developed a severe infection may indicate that it did not receive IgG specific for this pathogen, or that there are other host immunological mechanisms important in defence against this organism. The preponderance of experimental and clinical evidence in man indicates that type-specific humoral immunity is central to the prevention of pneumococcal infections. The source of the infection was not identified, but the most likely source was the dam of the foal or one of the people in contact with them. Although we know the mare was colonized by the organism at 5 days after parturition, we do not know if she was on Day I. If that were so, the foal may have been inoculated with a large dose of infective droplets from the dam's nasopharynx early in life. Conversely, the mare could have contracted the infection from her foal after he became ill. Immediately after admission to the VMTH and for the duration of his stay, however, the foal was kept separate from the mare. If we assume that the mare gave the infection to the foal, and not vice versa, the source of the mare's exposure was not identified. The organism could not be cultured from any other horse on the farm. The mare may have already been colonized upon arrival at the farm, or she may have been exposed to the bacteria From a nonequine source (man, dog etc.). The fact that two people in contact with the foal had upper respiratory tract disease might have been more than coincidence. Although the organism was not cultured from the farm manager's son or his assistant's nasopharynx, antibiotic therapy had been initiated before the cultures were taken. The possibility of transmission of S . penurnoniae from man to animal has previously been discussed. A cat developed septicaemia and septic arthritis due to S. pneurnoniae serotype 23F, and the same organism was cultured from a nasopharyngeal swab of the infant child that played with the cat (Stallings et al 1987). Reports of natural infection in calves causing pneumonia and in cows with mastitis were associated with humans suffering from respiratory tract infections (Donald and Mann 1950). During the foal's stay in hospital it became apparent that one of the most difficult aspects of his management would be keeping him from struggling while being mechanically ventilated. Various anaesthetics and sedatives were administered to the foal while he was on the ventilator. An ideal regimen would sedate the animal enough to keep him manageable and yet have a short half-life so that the animal's clinical state and level of awareness could be accurately evaluated. The most effective combination in this case was found to be detomidine and butorphanol, but the effectivenessof this regimen was short-lived and required many repeated doses. It would have been more desirable to have used a potent, longer acting, yet still readily reversible sedative with minimal cardiovascular depressant effects; unfortunately, such an agent was unavailable. Therapy of this foal was unsuccessful. In man, the mortality
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associated with neonatal pneumococcal infections is high. Despite sensitivity of the organism to several antibiotics, the overwhelming inflammatory reaction initiated by the pneumococcal cell wall is perpetuated even with the death of organisms (Tuomanen, Rich, and Zak 1987). In this case radiographic and blood gas data revealed no resolution of the initial insult. Although S. pneumoniue is a rarely recognised cause of infection in the neonatal foal, it should be considered in a neonate presenting with acute respiratory distress, radiographic signs of severe interstitial pneumonia and a history of interaction with humans with respiratory disease.
References Austrian. R. (1986) Some aspects of the pneumococcal carrier state. .I. Arifimicr. Ckem. 18. Suppl. A. 35-45. Benson, C.E. and Sweeney, C.R. (1984) Isolation of Streptococcus penumoniae Type 3 from equine species. J . d i n . Microhid. 20, 1028-1030. Burrell. M.H.. Mackintosh. M.E. and Taylor, C.E.D. (1986) Isolation of Streprococcus pneumoniue from the respiratory tract of hones. Equine wf.J. 18,
183.186 Donald. L.G. and Mann. S.D. (1950) Streptococcuspneumoniue infection in calves. Vef.Rec. 62.257-258. Gray, B.M.. Turner. M.E. and Dillon. H.C., Jr (1982) Epidemiologic studies of Sfreprococcus pneumoniue in infants (the effects of season and age on pneumococcal acquisition and carriage in the first 24 months of life). A m J. Epidemio/ogy 116.692-703. Guzzardo. M.B.. Hacker, M.E. and Walker. G. (1988) Neonatal pneumococcal pneumonia - case report and literature review. J. med. ASS".. GA. 77.313-31s. Harms. ER. (1941) Pneumokokkeninfektion beivii Rohlen. DocIi. Tieruerzfl. Wochenschr. 49. 10-13. Hoeprich, P.D. and Jordan. M.C. (1989) Infectious Diseuses - A Modern Treufise of' lnfecfiousProcesses. J.B. Lippincott Co.. Philadelphia. pp 374-388. Koterba. A.M.. Drummond. W.H. and Kosch, P.C. (1990) E4rrine Clinicol Nermufology. Lea & Febiger. Philadelphia. pp 177-191. Stallings. B.. Ling, C.V.. Lagenaur. L.A.. Jang. S.S. and Johnson, D.L. (1987) Septicemia and septic arthritis caused by Sfreprococcus pneumoniue in a cat: possible transmission from a child. J . Am. vef.med. Ass. 191.703-704. Tuomanen. E.. Rich, R. and Z a k . 0. (1987) Induction of pulmonary inflammation by components of the pneumococcal cell surface. Am. Rev. rcspir. Dis. 135. 869874.
Receivedfor publication: 29.4.91 Accepted: 30.1.92
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I 1
407
Equine vet. J . (1992) 24 ( 5 ) 407-410
Bacteraemia and pneumonia in a neonatal foal caused by Streptococcus pneumoniae J. C. MEYER, ANNE KOTERBA, G. LESTER and B. L. PURICH
Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida 326 10, USA.
Introduction STREPTOCOCCUS pneumoniue type 3 has been isolated from a tracheobronchial aspirate of a 6-month-old foal with pneumonia but other potentially pathogenic bacteria were cultured from the aspirate (Benson and Sweeney 1984). Isolation of S. pneumoniae from a 33-day-old foal with septic arthritis, pleuropneumonia, pericarditis and septicaemia has been reported, but the serotype of the isolate was not determined (Harms 1941). S . pneumoniue has been isolated from the respiratory tract of adult horses. A causal relationship between such isolates and respiratory disease has not been established (Benson and Sweeney 1984; Burrell, Mackintosh and Taylor 1986). Pneumococcal infections in man are most common in children and the aged. The predominant forms of such infections are pneumonia and meningitis often accompanied by bacteraemia and septicaemia. Factors that predispose to pneumococcal infection in adults include alcoholism, head injuries, and splenectomy. Pneumococcal infections in infants are sporadic, and associated with a high mortality rate (Guzzardo, Hacker and Walker 1988). Group B streptococcal infection is a more common cause of fulminating pneumonia and septicaemia amongst infants. This paper reports the clinical course of overwhelming pneumonia and bacteraemia caused by Streptococcus pneumoniae type 3 in a new born foal and efforts to identify the source of the infection.
Case history
weight was estimated at 5-7%. The mucous membranes were dark pink, capillary refill time was less than 2 sec, the quality of the pulse was good. Body temperature was 39.3"C, the heart rate 70-80 beats/min, and the respiratory rate 80-90 breathshin. The nostrils were flared, and there was a marked abdominal component to the breathing pattern. Thoracic auscultation revealed wheezes and crackles bilaterally, more pronounced over the ventral lung fields. Bilateral entropion and corneal ulceration were also noted.
Clinical pathology Because of the marked respiratory distress, the foal was immediately placed on nasal oxygen insufflation at 8 litres/min. Arterial blood gas analysis on supplemental oxygen revealed severe respiratory acidosis, mild metabolic acidosis, and hypoxaemia (Table I). The serum IgG concentration was > 800 mg/dl (CITE, IDEXX, Inc., Portland, ME, USA). The total white blood cell count was 1.2 x logflitre, with severe neutropenia (0.1 x lOg/litre), lymphopenia (0.74 x logflitre), and a degenerative left shift (0.19 x l09/litre bands, 0.070 x lo9 metamyelocytes/litre) with toxic changes. The PCV was 0.42 litresflitre, RBC count was 9.95 x IO**/litre, total plasma protein concentration 54 gflitre, and plasma fibrinogen concentration 5 ghitre. Reagent strip analysis of whole blood (Chemstrips, Boehringer Mannheim Diagnostics, Indianapolis, IN, USA) indicated hypoglycaemia (2.2 mmol/l). Serum electrolytes, BUN, and creatinine concentrations were within normal limits with the exception of those of sodium (129 mmol/litre), chloride (93 mmolflitre) and calcium (2.0 mmol/litre), which were low. Blood was withdrawn aseptically and cultured aerobically and anaerobically in Brucellu and Columbu blood culture broth. The broths were incubated at 37°C. Within 24 h, the aerobic culture
A 55-h-old, Thoroughbred colt of 335 days' gestational age was referred to the University of Florida Veterinary Medical Teaching Hospital (VMTH) with weakness of sudden onset and respiratory distress. The dam had been shipped to the breeding farm late in gestation and this was her first foal. The birth was attended, and the delivery process and fetal membranes were judged to be within normal limits. The foal stood and sucked within 2 h of birth, passed normal-looking meconium and behaved normally during the first 48 h of life. On the morning of the 3rd post-natal day the foal was found recumbent, dehydrated, and breathing rapidly. It was immediately shipped to the Veterinary Medical Teaching Hospital (VMTH).
TABLE 1: Blood values for the Infected foal
Physical examination
PH
On arrival at the VMTH the foal was weak and unable to stand without assistance. Body weight was 54 kg, and its nutritional state appeared adequate. Dehydration as a percentage of body
Procedure
Day 1 1O:OO h Supplemental 02
7.105
1 3 x 0 2 (mmHg) 74.5
Paop(mmHg) 40 HCO3- (mEqll) 23.6 BE (mEq/l) -7.0
Day 1 Day 1 Day2 1500 h 1O:OO h 10:43 h Manual Intermittent off ventilation mandatory ventilator with Ambu bag ventilation (03:OO h) 7.182 63.0 45 23.8 -5.1
7.385 41 .O 108 24.9 0.4
7.104 65.0 54.2 24.0
-5.2
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Fig I : Thoracic radiograph taken in lateral recumbency shortly after admission. There is a severe interstitial and alveolar pattern within the l ~ n and g vety little air present
Fig 2 : Luteral thoracic radiograph r,f' the fiml taken on Day 4 in hospital. The severity ofthe pulmonary infiltrate hus increased
was positive for S. pneumoniue. The organism appeared encapsulated, moist, mucoid, and transparent with colonies that tended to run together. Further identification was based on the Gram stain, alpha haemolysis, catalase reaction and optochin sensitivity. A subsequent culture of purulent material draining from an endotracheal tube was plated on Columbia agar with 5% sheep blood, Mackonkey agar, colistin/nalidixic acid agar with 5% sheep blood was incubated at 37°C in an atmosphere of air enriched with 5% C02. This culture also yielded a pure growth of S. pneumoniue with the same susceptibility pattern (ie susceptible to penicillin, ampicillin, cephalothin, erythromycin, co-trimoxazole, tetracycline, and ceftazidime but resistant to gentamycin as determined by the Kirby-Bauer method). both isolates were sent to The Center for Disease Control (Atlanta, Georgia, USA) for serotyping and were found to be of serotype 3. Based on these results the foal was treated with potassium penicillin G and ceftazidime. Chest radiography taken in lateral recumbency revealed a severe, diffuse interstitial and alveolar pattern throughout the lung fields (Fig I). The pattern appeared more pronounced in the antero-ventral view. These findings were consistent with a severe bacterial pneumonia.
became partly occluded with a copious purulent exudate, necessitating frequent clearing of the airway by suction. Over the first 24 h in hospital, the foal became much stronger and considerably less co-operative. Phenobarbital at a loading dose of 20 mg/kg iv was ineffective in adequately sedating the foal. Doses of xylazine, butorphanol and finally detomidine were administered frequently in an attempt to prevent struggling and accidental extubation. In spite of the use of these agents, it became increasingly difficult to maintain the foal on the ventilator. Periodic episodes of violent struggling resulted in fever spikes to over 40.2'C. These were controlled with alcohol, cold water baths and flunixin meglumine. After 26 h of mechanical ventilation, an attempt was made to remove the foal from the ventilator. Within 3 h severe respiratory acidosis and hypoxaemia recurred (Table I). The foal was therefore re-intubated and mechanical ventilation resumed. Peak inspiratory pressures at the same ventilator settings were 5 M cmH20. After being mechanically ventilated for another 20 h the foal was again disconnected from the ventilator. During the brief periods off the ventilator the foal was allowed to suck from a bottle. This provided inadequate nutritional support and consideration was given to beginning total parenteral nutrition. After the foal had been in hospital for 6 h, furosemide (50 mg, twice/day) was instituted to combat pulmonary oedema. In addition, after 24 h in hospital the foal received aminophylline (250 mg, 3 times/day). The furosemide therapy was discontinued after 48 h and the aminophylline therapy continued for the duration of the foal's stay. By 72 h after admission, the foal's WBC count had increased to 11.2 x IOgAitre, and plasma fibrinogen concentration had remained at 500 mg/dl, but his respiratory function appeared to be deteriorating further. He could not tolerate even brief periods without mechanical ventilation, and appeared to be weakening. When repeated chest radiographs revealed that the pulmonary infiltrates were worsening (Fig 2). permission was obtained for the foal to be destroyed.
Case management
Immediately after arterial blood gas results were obtained, a nasotracheal tube was passed, and the foal was manually ventilated by means of a I-litre AMBU bag supplied with supplemental oxygen. A balanced electrolyte solution and 5% (w/v) dextrose solution (Plasmalyte 148 with 5% dextrose, Baxter Healthcare Corp.) was infused as a continuous drip, and a broad-spectrum antibiotic regimen was instituted. Amikacin (7 mg/kg, 3 times/day), ampicillin (20 mg/kg, 4 times/day) and ceftazidime (20 mg/kg, 3 times/day) were administered pending bacteriological results. Manual ventilation only partly corrected the respiratory acidosis (Table I). Although the owner was given a very poor prognosis for the foal's survival, he requested that treatment be attempted. Intermittent mandatory ventilation was instituted by means of an Emerson volume-cycled ventilator. Machine settings of 12- 16 breathshin. tidal volume of 800 ml,as measured at the proximal endotracheal tube with a respirator, positive end - expiratory pressure (PEEP) of 5 cmH20, and fractional inspired oxygen (no2)of 0.8 generated a peak inspiratory pressure (PIP) of 40-60 cm H20 and maintained arterial blood gases within the normal range (Table I). Over the next 12 h, the FIO2 steadily decreased from 0.8 to 0.5, as Pao2 improved. The endotracheal tube often
Pathology
Grossly, the lungs were firm, mottled-red, and heavy. Microscopically, the cellular infiltrate in the interstitium comprised macrophages and hyperplastic type I1 pneumocytes. There were numerous alveoli and terminal bronchioles containing a deeply staining basophilic material. The morphological diagnosis was a severe, diffuse, subacute, interstitial pneumonia with associated intra-alveolar material. The intra-alveolar material
EQUINE VETERINARY JOURNAL
was thought to be milk or inhaled amniotic squamous cells. A Gram stain identified Gram-positive cocci associated with several vessels around alveoli. Cultures of lung, heart, blood and bone marrow did not yield any bacterial growth.
Epidemiology An attempt was made to determine the source of the infection. The uterus and nasopharyngeal region of the dam were swabbed 5 days post parturn. The uterine swab was negative for the organism, but the nasopharyngeal swab yielded a pure culture of S . pneumoniae type 3 (also serotyped at the Center for Disease Control, Atlanta, Georgia). The mare was treated with penicillin G (20,000 iu/kg, timedday) for 5 consecutive days. A nasopharyngeal swab obtained after the dose did not yield S. pneumoniae. Nasopharyngeal swabs were collected from 8 brood mares that had been in contact with the dam at the farm shortly before or after foaling. In addition, nasopharyngeal swabs were taken from 6 racehorses in training at the farm but which had no contact with the affected foal's dam. All 14 of these cultures were negative for S. pneumoniae. Three people had been in contact with the mare and foal; they were the farm manager, his son and an assistant. Before the foal's birth the assistant was being treated with antibiotics for an undiagnosed respiratory infection. Concurrent with the foal's illness the farm manager's son developed a cough and became febrile, requiring antibiotic therapy. The farm manager also developed a mild throat irritation. Sputum and throat cultures taken from the assistant and the farm manager's son after the antimicrobial therapy were negative.
Discussion S. pneumoniae is an alpha-haemolytic, Gram positive, lanceolate
coccus seen in pairs. Short chains of cocci are most commonly associated with serotype 3. There are 83 serotypes of S. pneumoniae which are capsular polysaccharides. The pneumococci are highly susceptible to physical agents such as heat and drying. Most strains of S. pneumoniae demonstrate striking susceptibility to penicillin G and erythromycin with rate clinical isolates being resistant. The mechanism of resistance to penicillin by some serotypes of S. pneumoniae is unknown, but it is not due to elaboration of betalactamase or R plasmids (Hoeprich and Jordan 1989). S. pneurnoniae is often found as a normal inhabitant of the upper respiratory tact of humans and it may be isolated from up to 60% of normal people (Austrian 1986). The rate of colonization varies with season, age and density of population (Gray, Tumer and Dillon 1982). S . pneumoniae is the most common cause of community-acquired pneumonia in humans. Classical pneumococcal pneumonia in the adult strikes suddenly. The victim develops a shaking chill which leads to a sustained fever. A productive cough producing rusty mucopurulent sputum develops. The patient often develops pleuritis and pulmonary consolidation. The disease is noted for its dramatic and sudden onset. The prognosis for recovery in adults with antimicrobial therapy is good provided there is no underlying disease which adversely affects pulmonary defence mechanisms (Hoeprich and Jordan 1989). By contrast, the disease in children is sporadic and associated with a high mortality rate (Guzzardo et a1 1988). S . pneurnoniae accounts for only 5 % of the cases of neonatal bacteraemia. The foal in this report had a severe, acute bronchopneumonia and severe respiratory distress. The radiographic changes in this case were suggestive of either severe bacterial pneumonia or hyaline membrane disease (HMD) (Koterba, Drummond and Kosch 1990). However, HMD was considered unlikely because the foal was born at term, and signs of respiratory distress did not appear until Day 3 of age. Culturing the blood and tracheal secretions was useful in reaching a specific diagnosis. Recent reports focus on the isolation of S. pneurnoniae from
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the upper respiratory tract of adult horses and do not provide direct evidence to implicate the isolation of this organism with disease (Benson and Sweeney 1984; Burrell et al 1986). There appears to be an asymptomatic carrier state in horses (Burrell et al 1986). However, the low incidence of recovery of S. pneumoniae from horses compared with humans suggests that the horse acquires the microbe from humans rather than acting as a reservoir for human infection (Benson and Sweeney 1984). One perplexing question in this case is why the foal acquired this particular type of infection. This was the first time that S. pneumoniae had been isolated from a neonatal foal admitted to our hospital. We considered that an infection acquired in utero was unlikely. The foal was born at term and appeared of normal size, the placenta appeared grossly normal, and the foal appeared clinically normal until Day 3 of life. The foal also seemed at low risk of becoming infected post parturn. There were no problems noted at birth, the foal had a normal serum concentration of IgG at 24 h of age, and he appeared vigorous and strong. However, on the basis of clinical signs and the history, it is most likely that he did acquire the infection following birth. The fact that the foal appeared to have an adequate amount of IgG and yet developed a severe infection may indicate that it did not receive IgG specific for this pathogen, or that there are other host immunological mechanisms important in defence against this organism. The preponderance of experimental and clinical evidence in man indicates that type-specific humoral immunity is central to the prevention of pneumococcal infections. The source of the infection was not identified, but the most likely source was the dam of the foal or one of the people in contact with them. Although we know the mare was colonized by the organism at 5 days after parturition, we do not know if she was on Day I. If that were so, the foal may have been inoculated with a large dose of infective droplets from the dam's nasopharynx early in life. Conversely, the mare could have contracted the infection from her foal after he became ill. Immediately after admission to the VMTH and for the duration of his stay, however, the foal was kept separate from the mare. If we assume that the mare gave the infection to the foal, and not vice versa, the source of the mare's exposure was not identified. The organism could not be cultured from any other horse on the farm. The mare may have already been colonized upon arrival at the farm, or she may have been exposed to the bacteria From a nonequine source (man, dog etc.). The fact that two people in contact with the foal had upper respiratory tract disease might have been more than coincidence. Although the organism was not cultured from the farm manager's son or his assistant's nasopharynx, antibiotic therapy had been initiated before the cultures were taken. The possibility of transmission of S . penurnoniae from man to animal has previously been discussed. A cat developed septicaemia and septic arthritis due to S. pneurnoniae serotype 23F, and the same organism was cultured from a nasopharyngeal swab of the infant child that played with the cat (Stallings et al 1987). Reports of natural infection in calves causing pneumonia and in cows with mastitis were associated with humans suffering from respiratory tract infections (Donald and Mann 1950). During the foal's stay in hospital it became apparent that one of the most difficult aspects of his management would be keeping him from struggling while being mechanically ventilated. Various anaesthetics and sedatives were administered to the foal while he was on the ventilator. An ideal regimen would sedate the animal enough to keep him manageable and yet have a short half-life so that the animal's clinical state and level of awareness could be accurately evaluated. The most effective combination in this case was found to be detomidine and butorphanol, but the effectivenessof this regimen was short-lived and required many repeated doses. It would have been more desirable to have used a potent, longer acting, yet still readily reversible sedative with minimal cardiovascular depressant effects; unfortunately, such an agent was unavailable. Therapy of this foal was unsuccessful. In man, the mortality
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associated with neonatal pneumococcal infections is high. Despite sensitivity of the organism to several antibiotics, the overwhelming inflammatory reaction initiated by the pneumococcal cell wall is perpetuated even with the death of organisms (Tuomanen, Rich, and Zak 1987). In this case radiographic and blood gas data revealed no resolution of the initial insult. Although S. pneumoniue is a rarely recognised cause of infection in the neonatal foal, it should be considered in a neonate presenting with acute respiratory distress, radiographic signs of severe interstitial pneumonia and a history of interaction with humans with respiratory disease.
References Austrian. R. (1986) Some aspects of the pneumococcal carrier state. .I. Arifimicr. Ckem. 18. Suppl. A. 35-45. Benson, C.E. and Sweeney, C.R. (1984) Isolation of Streptococcus penumoniae Type 3 from equine species. J . d i n . Microhid. 20, 1028-1030. Burrell. M.H.. Mackintosh. M.E. and Taylor, C.E.D. (1986) Isolation of Streprococcus pneumoniue from the respiratory tract of hones. Equine wf.J. 18,
183.186 Donald. L.G. and Mann. S.D. (1950) Streptococcuspneumoniue infection in calves. Vef.Rec. 62.257-258. Gray, B.M.. Turner. M.E. and Dillon. H.C., Jr (1982) Epidemiologic studies of Sfreprococcus pneumoniue in infants (the effects of season and age on pneumococcal acquisition and carriage in the first 24 months of life). A m J. Epidemio/ogy 116.692-703. Guzzardo. M.B.. Hacker, M.E. and Walker. G. (1988) Neonatal pneumococcal pneumonia - case report and literature review. J. med. ASS".. GA. 77.313-31s. Harms. ER. (1941) Pneumokokkeninfektion beivii Rohlen. DocIi. Tieruerzfl. Wochenschr. 49. 10-13. Hoeprich, P.D. and Jordan. M.C. (1989) Infectious Diseuses - A Modern Treufise of' lnfecfiousProcesses. J.B. Lippincott Co.. Philadelphia. pp 374-388. Koterba. A.M.. Drummond. W.H. and Kosch, P.C. (1990) E4rrine Clinicol Nermufology. Lea & Febiger. Philadelphia. pp 177-191. Stallings. B.. Ling, C.V.. Lagenaur. L.A.. Jang. S.S. and Johnson, D.L. (1987) Septicemia and septic arthritis caused by Sfreprococcus pneumoniue in a cat: possible transmission from a child. J . Am. vef.med. Ass. 191.703-704. Tuomanen. E.. Rich, R. and Z a k . 0. (1987) Induction of pulmonary inflammation by components of the pneumococcal cell surface. Am. Rev. rcspir. Dis. 135. 869874.
Receivedfor publication: 29.4.91 Accepted: 30.1.92
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