A captive-born 1-year-old 9-kg (19.8-lb) female reticulated python (Python reticulatus) was evaluated by a primary care veterinarian because of a 2-week history of wheezing and hissing loudly. The owner reported that the snake was fed live rats weighing from 0.375 to 0.475 kg (0.825 to 1.045 lb) every 2 weeks. On initial evaluation, the veterinarian noted clogged nares and suspected respiratory disease. There were also several puncture wounds along the snout, indicative of traumatic injury likely resulting from interactions with live prey. Evaluation of radiographs revealed no evidence of pulmonary disease; however, interpretation of the radiographic appearance of skull bones was inconclusive. Administration of ceftazidime (20 mg/kg [9.1 mg/lb], IM, q 72 h) was initiated for treatment of rat bite trauma. The snake was referred to a veterinary teaching hospital for further evaluation.
On evaluation at the teaching hospital 7 days after the examination that led to referral, loud hissing sounds associated with breathing were noted. Severe facial cellulitis was evident, and tissues within the nares were swollen, resulting in an audible wheeze during respiration at rest. The owner reported seeing the python forcefully press its face repeatedly against the glass of its enclosure. The snake had scars attributed to rat bites along the length of its body, with more recent, unhealed injuries along the snout. A 5-mm-long, 3-mm-deep gingival pocket associated with 3 missing rostral left maxillary teeth was identified on oral examination (Figure 1). Judging from the presence of dry oral and cloacal mucous membranes, the snake was presumed to be mildly to moderately dehydrated.
Photograph showing a deep gingival pocket associated with 3 missing rostral left maxillary teeth in a 1-year-old female tiger reticulated python (Python reticulatus) that was evaluated because of a 2-week history of wheezing and hissing.
Citation: Journal of the American Veterinary Medical Association 248, 9; 10.2460/javma.248.9.1027
A handheld dental radiography machinea was used to obtain dorsoventral views of the skull in the unsedated patient. Radiography revealed a distinct lucency of the rostral left aspect of the maxilla corresponding to the site of the missing teeth; changes suggestive of bony lysis of the right maxilla, consistent with osteomyelitis, were also observed. A CBC revealed leukocytosis (13.80 × 103 leukocytes/L; reference range, 3.4 × 103 leukocytes/L to 12.6 × 103 leukocytes/L),b characterized by presumed (on the basis of mammalian data) marked monocytosis (8.42 × 103 monocytes/L [61%]; reference range unknown). Plasma biochemical analysis revealed hyperkalemia (8.2 mmol/L; reference range, 4 to 7 mmol/L).b
The python was hospitalized for 2 days. The owner declined microbial culture of the gingival lesions. Treatments included ceftazidime (20 mg/kg, IM, q 72 h); meloxicam (0.2 mg/kg [0.09 mg/lb], IM, q 48 h); fluid therapy with a multiple electrolyte solutionc (20 mL/kg, SC, once); warm-air nebulization with saline (0.9% NaCl) solution for 20 minutes 3 to 4 times daily; lavage of the oral pocket with 0.75% chlorhexidine solution, once; and topical application of 1% silver sulfadiazine cream to wounds along the snout every 48 hours. Within 2 days after treatment was initiated, the cellulitis was noticeably reduced. The patient was discharged from the hospital with instructions for the owner to continue ceftazidime and meloxicam administration at the prescribed dosages for 14 days, to increase enclosure humidity (from 20% to 50%), and to provide improved thermal gradients within the enclosure (80° to 95°F). Feeding thawed frozen rodents, instead of live prey, was advised.
At a follow-up examination 3 weeks after the initial referral examination, the owner reported that the hissing had resolved and that the python showed an interest in food but had not eaten since the initial evaluation. Weight loss (from 9.0 to 8.85 kg [19.8 to 19.5 lb]) was noted on physical examination, and the superficial bite marks on the snout had begun to heal. The gingival lesion was larger than previously noted, characterized as 10 mm wide with a depth > 5 mm. Dental radiography revealed an approximately 10-mm area of bony lysis within the rostral segment of the left maxilla, with an additional lytic lesion at the most rostral aspect of the right maxilla (Figure 2). At this time, the owner elected to pursue the recommended CBC, plasma biochemical analysis, and surgical management of the oral lesions, with microbial culture of blood and bone samples and histologic evaluation of affected tissues.
Dorsoventral radiographic views of the skull of the python in Figure 1 before (A) and after (B) bilateral partial maxillectomies. A—Notice radiographic evidence of lysis at the most rostral aspects of the maxillae. Arrows indicate areas of bone lysis. B—In the postoperative radiographic image, arrows indicate the sites of bone resection. L = Left. R = Right.
Citation: Journal of the American Veterinary Medical Association 248, 9; 10.2460/javma.248.9.1027
Plasma biochemical analysis revealed a high total protein concentration (8.9 g/dL; reference range, 6.3 to 8.7 g/dL) and hyperkalemia (8.4 mmol/L). A CBC revealed marked leukopenia (1.32 × 103 leukocytes/L) and presumed persistent monocytosis (0.70 × 103 monocytes/L [53%]). Cell morphology appeared normal; however, septicemia was strongly suspected despite the absence of morphological changes. Preoperative microbial culture of a blood sample grew scant amounts of coagulase-negative, gram-positive cocci and of Bacillus spp, which were not identified because of suspected sample contamination; therefore, bacteremia was not conclusively diagnosed before surgery.
Anesthesia was induced with butorphanol (1.5 mg/kg [0.68 mg/lb], IM) and ketamine (10 mg/kg [4.5 mg/lb], IM). The snake was intubated, and anesthesia was maintained with isoflurane (2% to 2.5%) in oxygen; intermittent positive-pressure ventilation was provided at 20 breaths/min for the duration of the surgery. Respiratory rate, heart rate, and cloacal temperature were monitored. The snake was coiled into a comforter, and multiple forced-air warming unitsd were used to maintain ambient temperatures ranging from 29.4° to 32.2°C (85° to 90°F) in the operating room during surgery. Local anesthesia was provided by infiltration of lidocaine (2.2 mg/kg [1 mg/lb]) and bupivacaine (0.5 mg/kg [0.23 mg/lb]) along the buccal aspect of the gingiva. Periosteal nerve blocks were performed along the length of the affected regions of the left and right maxilla and caudal to each lesion (by a distance of approx 3 teeth). Meloxicam (0.2 mg/kg, IM) was administered perioperatively for analgesia.
A 5.1-cm-long horizontal incision was made along the lateral aspect of the left maxilla over the affected bone. A high-speed (250,000 to 350,000 rpm) dental handpiecee on an oil-free dental compressor unitf was used with a cross-cut fissure burg to resect the affected bone from the buccal to the lingual aspect. After resecting the affected mucosa, the mucosal defect was closed with 5-0 polydioxanone in a simple interrupted pattern. The same approach was used to complete removal of the affected right rostral segment. Approximately 5.1 cm of bone was removed from the left maxilla, and 3.8 cm was removed from the right maxilla. Dorsoventral dental radiographs were obtained after surgery (Figure 2) to confirm complete resection of the affected maxillary segments. The snake was routinely monitored during recovery from anesthesia, which was uneventful.
Histopathologic findings of the left maxillary bone included chronic active osteomyelitis with multifocal osteonecrosis and bone remodeling (Figure 3). A single focus of severe inflammation, characterized by heterophilic inflammation and aggregates of epithelioid macrophages surrounded by proliferating fibroblasts, was identified within the bone marrow space. Within this focus, there were necrotic bone spicules and large numbers of gram-positive cocci, which were considered morphologically consistent with the bacteria identified on examination of the preoperative blood sample.
Photomicrographs showing sections of resected bone from the left maxilla of the python in Figure 1. A—A single focus of heterophilic and granulomatous inflammation surrounded by proliferating fibroblasts (asterisk) is evident within the bone marrow space. H&E stain; bar = 200 μm. B—On higher magnification of the inflammatory focus in panel A, hypereosinophilic necrotic bone spicules that have scalloped edges and lack osteocytes within the lacunae are present (asterisk). The necrotic bone spicules are encircled by epithelioid macrophages, a few heterophils, and proliferating fibroblasts. H&E stain; bar = 50 μm. C—Notice numerous gram-positive cocci within the inflammatory focus in the bone marrow space. Gram stain; bar = 10 μm.
Citation: Journal of the American Veterinary Medical Association 248, 9; 10.2460/javma.248.9.1027
Aerobic and anaerobic microbial culture of the resected maxillary bone yielded Staphylococcus sciuri, Enterococcus faecalis, and Stenotrophomonas maltophilia. The S sciuri isolate was resistant to penicillins but susceptible to fluoroquinolones. The S maltophilia isolate was resistant to ticarcillin, ceftazidime, and fluoroquinolones. All isolates were susceptible to gentamicin and TMS. During hospitalization, an injectable formulation of TMSh was administered (30 mg/kg [13.6 mg/lb], IM, q 24 h) and treatment with meloxicam (0.2 mg/kg, IM, q 48 h) was continued. The patient ate 48 hours after the surgical procedure and was subsequently discharged from the hospital; the owner was given instructions to continue meloxicam (for another 5 days) and TMS (for 6 weeks) at the prescribed dosages. The owner was advised to feed 2 or 3 rodents (of smaller sizes than previously offered) for a meal after 7 days. A postoperative follow-up examination 7 to 10 days after hospital discharge was recommended; however, this did not take place.
Four months after the surgery, the python was evaluated because of obstipation and rubbing of its face along the wall of its enclosure. The patient weighed 13.1 kg (28.8 lb) but was mildly dehydrated. The surgical sites had healed. A blood sample was collected for CBC and plasma biochemical analysis. Leukopenia (2.2 × 103 leukocytes/L), characterized by suspected monocytosis (0.64 × 103 monocytes/L [29%]), was present. Plasma biochemical analysis revealed a high total protein concentration (11.4 g/dL). Radiographs (dorsoventral views) were obtained as previously described and revealed small, focal lytic changes on the left aspect of the premaxilla. Microbial culture of a blood sample and another surgical intervention were recommended. The owner agreed to 1 SC fluid treatment as administered previously and elected to initiate empirical treatment with TMS as previously prescribed for 6 weeks. Husbandry improvements were discussed, and ambient temperature recommendations had been met; the owner agreed with further recommendations to additionally use a warm water humidifier unit near the enclosure and to continue with weekly soaking in a basin to improve the snake's hydration status.
Eight months after surgery, the patient was reevaluated because of continued facial rubbing and recurrent facial cellulitis. The snake's weight was 17.66 kg (38.9 lb). A blood sample was collected; results of a CBC revealed that the total WBC count was within the reference range (6.48 × 103 leukocytes/L), with 4.53 × 103 monocytes/L (70% monocytes). No evidence of toxic changes was found on morphological evaluation of a blood smear. Plasma biochemical analysis revealed a high total protein concentration (11.4 g/dL). Radiography was repeated as described, and new distinct areas of bony lysis were identified on the left and right aspects of the premaxilla (Figure 4). A gingival pocket was identified that corresponded to the site of radiographic abnormalities. The owner approved a second surgical intervention to remove the affected premaxilla.
Dorsoventral radiographic view of the skull of the python in Figure 1 obtained 8 months after bilateral partial maxillectomies were performed. Progressive lytic lesions of the premaxilla are evident (arrow). L = Left. R = Right.
Citation: Journal of the American Veterinary Medical Association 248, 9; 10.2460/javma.248.9.1027
The python was anesthetized with the previously described protocol, with minor adjustments, which included an increase in the dose of butorphanol to 2.0 mg/kg (0.91 mg/lb), IM, and addition of midazolam (0.1 mg/kg [0.045 mg/lb], IV) to the induction protocol. Local anesthesia was provided by infiltration of anesthetic agents into the affected soft tissue, and a periosteal nerve block was performed along the ventral aspect of the vomer, with lidocaine and bupivacaine doses as previously described. Blunt dissection was used to remove tissue attachments from the affected bone. An oscillating dental sawi was used for resection of the bone in an effort to minimize nerve damage. After the premaxilla was removed, little remaining rostral mucosa remained, and the site was closed with 5-0 poliglecaprone 25 in a simple interrupted suture pattern. Aerobic and anaerobic microbial culture of the premaxilla revealed Escherichia coli, Proteus spp, and E faecalis. All isolates were susceptible to fluoroquinolones, gentamicin, and TMS. Warm hypotonic saline (0.45% NaCl) solution was administered into the cloaca for fluid therapy prior to the python's discharge from the hospital, and continuation of the TMS treatment for a period of 8 weeks, administration of meloxicam for 3 days after surgery, and follow-up examination in 7 days were recommended. The owner returned with the python for a follow-up visit in 2 weeks, noting that the snout-rubbing behavior had returned. The patient's weight had decreased, compared with findings for the previous visit, to 16.2 kg (35.6 lb). There was wound dehiscence at the surgical site with areas of caseous debris and some granulation tissue. The snake was anesthetized following the same protocol used for the premaxillectomy procedure, and the area was debrided. Horizontal mattress sutures, in addition to simple interrupted sutures, were used in closing the gingival tissue to relieve some of the tension at the rostral aspect of the wound.
Three months after the second surgery, the snake was returned to the teaching hospital because of obstipation. The surgical site was almost healed, and the owner agreed to advanced diagnostic imaging to confirm there was no remaining oral disease. A CBC revealed leukocytosis (19.6 × 103 leukocytes/L) with suspected lymphocytosis (11.48 × 103 lymphocytes/L [59%]; reference range unknown), no evidence of monocytosis (count of 0.2 × 103 monocytes/L [1%]), and no toxic changes observed on morphological examination. Anesthesia was induced with midazolam (0.1 mg/kg, IM), butorphanol (1 mg/kg [0.45 mg/lb], IM), and ketamine (10 mg/kg, IM) and maintained with isoflurane at 1.5% to 2.25%. The python was placed in ventral recumbency, and CT images of the head and body were obtained in coronal and sagittal planes by use of a scannerj in helical acquisition mode (rotation time, 0.9375 seconds; voltage, 100 kV; and amperage, 160 mA). Multiplanar reconstructions were generated on a dedicated CT workstation.k The CT images revealed no evidence of residual osteomyelitis (Figure 5) but confirmed retained fecal material in the aborad aspect of the colon. The patient was given a warm hypotonic saline solution cloacal enema and released from the hospital; increased humidity of the patient's enclosure at home (to 75%) was recommended to improve husbandry. For 12 months after the CT, regular follow-up was maintained by telephone calls with the owner, who reported that the patient had returned to its regular feeding behavior, activity level, and defecation frequency.
Left lateral (A), right lateral (B), and dorsoventral (C) 3-D reconstructed CT images of the skull of the python in Figure 1 obtained 11 months after initial partial maxillectomy and 3 months after surgical removal of the premaxilla. Arrows indicate sites of bone resection. No evidence of osteomyelitis is apparent.
Citation: Journal of the American Veterinary Medical Association 248, 9; 10.2460/javma.248.9.1027
Discussion
Facial nerve anatomy, maxillary sensory nerve anatomy, prey-capture mechanisms for large boids, and boid skull morphology and function were carefully reviewed to develop a surgical approach that would maximize the chance for postoperative feeding success for the patient of this report. Review of available information on maxillary sensory nerve anatomy in reticulated pythons revealed that trigeminal nerve extensions lie superficially in the infralabial scales at a depth of 15 μm in this species.1 Given the superficial depth of the infralabial nerve extensions, injury of these trigeminal nerve branches could be avoided by use of a lateral and palatine approach for surgical resection of maxillary segments. In the event of iatrogenic nerve damage, feeding behavior may not be completely compromised. Investigators of a study1 of Boa constrictors (Boa constrictor constrictor) and Burmese pythons (Python molurus) determined that prey-capture success is based on visual, thermal, chemosensory, and mechanical sensation of prey. A single visual stimulus was found to be the most important factor to elicit hunting behavior in pythons. Boids were less dependent on thermal, chemical, and mechanical stimuli than on visual stimuli. When the labial pits (which allow for precise body heat detection of prey) of boid snakes were physically blocked and sight was not blocked, there was more hunting behavior observed than when both the eyes and labial pits were blocked. The python of the present report had been conditioned to accept dead prey as food, which confirmed visual prey-capture behavior prior to surgery, and feeding continued to be successfully triggered with visual stimulus after oral surgery.
Additional anatomic considerations for locoregional anesthesia were assessed prior to the initial surgery in the patient of this report. The trigeminal nerve extensions exit from an anterior prootic foramen in reticulated pythons.2 An infraorbital nerve block, which is commonly performed in canine and feline patients prior to dental extractions, was avoided because of the risk of additional injury, given the location of the nerve relative to the orbit. The palatine nerve arises from the facial nerve and travels ventrolaterally along the roof of the palate to reach the vomeronasal organ.3 To avoid damage to the vomeronasal organ, periosteal blocks were performed on the lateral aspects of the maxillary bones.
Maxillary alterations could have impacted grasping success and ingestion of prey after surgery. Evaluation of Burmese pythons and African rock pythons (Python sebae) revealed 2 important features regarding jaw mechanics associated with prey capture.4 First, the skull of boids is very flexible, and protraction of the palatomaxillary arches results in lateral expansion of the maxilla and a medial pterygoid shift that clinches the palatine teeth. Second, the premaxillary and rostral maxillary teeth are the most important for initial prey seizure, especially for larger prey items. However, when small prey is seized, it is often taken far back into the mouth where the more posterior palatine teeth can engage it. The results for the python of this report supported that prey capture could still be achieved with the palatine teeth after surgical resection of the premaxillary bone and rostral maxillary segments. In this case, feeding of smaller rodents was recommended after oral surgery. The python had eaten rats that weighed 0.375 to 0.475 kg before it sustained injury and did not have any difficulty consuming rats that weighed 0.175 to 0.275 kg (0.39 to 0.605 lb) after bilateral partial maxillectomies and premaxillectomy.
Antimicrobials administered after surgery were selected on the basis of microbial culture results for bone samples from the python of this report. There are limited pharmacokinetic studies of antimicrobials in snakes. Prior to microbial culture of samples from the affected tissues, ceftazidime, a third-generation cephalosporin used in snakes,5 was empirically selected on the basis of several reports6–8 indicating that gram-negative flora are the predominant bacteria in the oral cavity of snakes. Fluoroquinolone,9,10 aminoglycoside,11,12 and β-lactamase13 antimicrobials were considered but not administered because of resistance patterns identified in organisms cultured from the patient of this report, poor efficacy in a pharmacokinetic study,13 and reports14–17 of nephrotoxicity, respectively. Chloramphenicol was also considered because of a single-dose study18 that revealed a 50 mg/kg (22.72 mg/lb) dose, IM, resulted in serum concentrations of 2 to 5 μg/mL in Burmese pythons. However, treatment of the E faecalis culture isolate from our patient would have required therapeutic circulating concentrations > 8 μg/mL, and administration of chloramphenicol was not pursued. The isolates from maxillary bones were resistant to ceftazidime and fluoroquinolones; isolates cultured from premaxillary bone were identified as susceptible to both of these drugs, but neither was used because of resistance detected in the earlier maxillary bone cultures. Ceftazidime resistance of Stenotrophomonas spp isolated from reptiles has been increasingly reported in the literature.8,19 A long-acting ceftiofur formulation that is effective against Proteus spp and E coli has been evaluated in ball pythons (Python regius).20 Historically, ceftiofur has had variable in vitro efficacy against Staphylococcus spp and Stenotrophomonas spp20,21
Although culture and susceptibility testing results indicated that E faecalis isolated from the python of this report was susceptible to TMS, authors of 1 report22 found that TMS was not effective against E faecalis. In the case described in the present report, progressive infection of the maxilla and premaxilla with organisms including E faecalis was identified. In preparation for the premaxillectomy, E faecalis was suspected as a cause of persistent osteomyelitis on the basis of results for bacterial culture. Because antimicrobial treatment alone did not resolve the maxillary osteomyelitis, this led to the decision that complete surgical removal of the affected premaxilla bone was the best treatment approach. Although it was not included in the susceptibility tests for isolates from our patient, results of a study23 performed to evaluate pharmacokinetics of piperacillin (100 mg/kg [45.5 mg/lb], IM, q 24 h) in blood pythons (Python curtus) supported its use as an adjunctive treatment if recurrence of soft tissue infection with E faecalis was identified after premaxillectomy.
There are few reports24,25 available on the use of sulfonamides in the treatment of reptiles; however, doses extrapolated from studies of mammalian26 and avian species27 are described in a formulary for exotic animal species.28 Authors of 1 study24 investigated TMS as an anticryptosporidial medication in snakes. Variable TMS resistance patterns have been described for Stenotrophomonas spp in the human and veterinary literature29; however, successful treatment of chronic Stenotrophomonas-associated osteomyelitis in a human patient with prolonged administration of high doses of TMS has been reported.30 Reported adverse reactions following administration of TMS in mammals include keratoconjunctivitis sicca, liver failure, thrombocytopenia, and potential hypersensitivity reactions.26 No apparent adverse effects were observed in the patient of this report.
Serial CBCs were performed to identify systemic changes associated with confirmed bacteremia and active osteomyelitis. The WBC morphology was not indicative of sepsis; however, the presence of leukopenia provided the impetus to perform oral surgery when systemic antimicrobial treatment failed to resolve maxillary and premaxillary osteomyelitis. The chronicity of oral disease was characterized by persistent presumed monocytosis that completely resolved following surgical removal of affected bone. Serial microbial cultures of the blood, declined by the owner, would have been ideal to establish whether the selected antimicrobial dosage achieved clinically effective minimum inhibitory concentrations to treat the presumed bacteremia noted just before the first surgery.
Evidence-based review of ophidian cranial nerve anatomy, skull morphology and function, speciesspecific surgical planning, postoperative monitoring, and culture-based antimicrobial selection contributed to the postoperative recovery and clinical outcome for the patient described here. Historically, a grave to fatal prognosis has been associated with severe stomatitis and progressive osteomyelitis in snakes.31–34 Focal rostral maxillary and premaxillary osteomyelitis in large boid species can be surgically managed if detected before widespread osteomyelitis occurs. Owing to bone involvement, sepsis from acquired bacteremia should be suspected in these cases, and microbial culture of blood is indicated. Antimicrobials should be selected on the basis of microbial culture results whenever possible, considering that antimicrobial resistance to commonly used chemotherapeutics has been reported.8,19 Gram-positive flora can serve as causative agents of oral disease in snakes, as in the patient of this report, and the oral flora of rodent prey34,35 can also infect wounds sustained from severe rat bite trauma to the face in snakes.
ABBREVIATIONS
| TMS | Trimethoprim-sulfamethoxazole |
Footnotes
Nomad, Aribex Inc, Orem, Utah.
ISIS Physiological Data Reference Values Project, Apple Valley, Minn: International Species Information System (ISIS), 2013.
Normosol-R, Hospira Inc, Lake Forest, Ill.
Bair Huger warming units, model 505, Arizant Healthcare Inc, Saint Paul, Minn.
C-type handpiece, 4 hole, Henry Schein, Plainview, NY.
iM3 Pro 2000 dental unit, iM3, Vancouver, Wash.
FG carbide cross cut fissure bur No. 702, Miltex, York, Pa.
TMS, 540 mg/mL injectable formulation, Best Pet Rx Pharmacy, New York, NY.
Piezotome, Salvin Dental Specialties Inc, Charlotte, NC.
GE BrightSpeed, General Electric Co, Milwaukee, Wis.
Advantage Workstation VolumeShare 2, General Electric Co, Milwaukee, Wis.
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