D. Mader
Medicine, Surgery and Wildlife, Marathon Veterinary Hospital, Marathon, FL, USA
Most of the antimicrobial research in herps has been limited pharmacokinetic, not pharmacodynamic studies. What that means is that although several drugs have been evaluated in several different herp species, only drug levels and suggested dosages have been evaluated, not the actual effect on the patient or the pathogens within the patient. Also to note, what little information that is available shows that different species respond differently to the same drug at the same dosages. So we may know, based on limited research, that you should give a snake a loading dose of 5.0 mg/kg of Amikacin, followed by 2.5 mg/kg every 72 hours, we actually have no idea what effect it has on the animal’s physiology or even it is going to work to rid the infection. There are a number of factors that must be considered when choosing an antibiotic. The results of microbiological culture and sensitivity testing, the species being treated, physical condition of the patient, frequency of administration, cost of the therapy, owner compliance, and a host of other factors are all important.
The veterinary clinician must have a thorough understanding of reptile physiology and biology prior to administering medications. Since all reptiles are ectotherms, and their metabolism is temperature dependent, they will often react unpredictably to the same drug in different settings. A good working knowledge of the more common species of reptiles, their life histories and their peculiarities will help prevent potential disasters during therapy.
General Considerations
Dehydrated or hyperuricemic patients should be properly rehydrated prior to initiating therapy. It is the rare case that cannot wait one to two days to assure appropriate hydration prior to treatment. However, if for some reason treatment must be instigated immediately, it would behoove the practitioner to choose a non-nephrotoxic drug.
Pharmacokinetic studies have shown that an increase in ambient temperature tends to increase both the volume of distribution and body clearance of the drug. A decrease in ambient temperature with a resultant decrease in body clearance could potentially allow a buildup in concentration of the drug to a point where it might reach toxic levels if dosing is not decreased accordingly.
When reptile pathogens are treated at higher temperatures, the mean inhibitory concentration (MIC) needed to achieve effective treatment significantly decreases. This allows for a lower dose of antibiotic to be given, another positive factor when dealing with potentially nephrotoxic drugs.
Most researchers feel that it is best to treat sick reptiles near the higher end of their preferred optimum temperature zone. Not only is it beneficial for reasons already mentioned, but elevated ambient temperatures have been shown to stimulate the host’s immune system and aid in fighting disease in other ways already discussed.
In critically ill or immuno-compromised reptiles, bactericidal, rather than bacteriostatic antibiotics, are preferable. In cases of gram-negative sepsis, especially with Pseudomonas infections, the reptile patient is often severely immunocompromised.
In many cases, the animals are infirmed because they have been immunocompromised due to improper husbandry conditions. The most common cause is from being maintained at suboptimal environmental temperatures.
Methods of Administration
There are very few instances where oral antibiotic therapy is required. Enteric infections often warrant oral administration of appropriate drugs. There are two common methods for administering oral antibiotics. If the patient is still feeding, the antibiotic can be mixed with the food or injected into the dead prey and fed to the animal. Gavaging, or stomach tubing, is a second technique which can be used to administer oral medications.
Topical Antibiotic Therapy
Although oral dosing of systemic antibiotics is not commonly done, it is not uncommon to actually treat the oral cavity itself. This is often done in cases of severe infectious stomatitis, where the oral cavity is abscessed.
Since the vascularity to an abscessed oral cavity is usually compromised, antibiotics given systemically may not be able to reach adequate therapeutic levels in the infected tissues. Aminoglycoside antibiotics have decreased activity in anaerobic or acidic environments. When treating with a drug like enrofloxacin systemically, you can also use topical fluoroquinolone on the lesions in the oral cavity. Daily application of Ciloxin® ophthalmic solution, one drop on each affected area, works well.
Silvadene® is a soft, white, water-miscible cream containing the antimicrobial agent silver sulfadiazine. This bactericidal cream is effective against a broad range of both gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa, as well as some of the yeasts. Silvadene® is easily applied with a cotton tipped swab or other applicator. A dressing is not necessary unless the area being treated is in a location where the cream may be rubbed off. Otherwise, the cream will last for two to three days before a new application is required.
Injectable Antibiotic Therapy
Injectable antibiotics are probably the best form for assuring proper delivery of the drug. The antibiotics are either injected intramuscularly, or less commonly, subcutaneously. The intravenous route is often limited by the availability of venous access. The size and species being treated will determine whether intravenous infusion is possible.
An important consideration when selecting an antibiotic is its ability to penetrate the target tissue site. In cases of severe Infectious Stomatitis, the vascular supply may be compromised to the oral cavity in the area of the lesions. This may prevent good penetration of the antibiotic to the site of infection.
Another method of assuring adequate antibiotic levels to the affected tissue is to calculate the total systemic dose, draw it into a syringe, and then add an equal volume of bacteriostatic water to dilute it out to half concentration. Inject three-fourths of the dose intramuscularly, and the remaining quarter dose directly into the region of the mouth where the infection is present. If you need to inject in more than one place in the mouth it is a good idea to switch needles to prevent seeding of bacteria from one site to another.
Renal and Hepatic Portal Systems
Reptiles have both renal and hepatic portal systems. Thus, unless it is known how the particular drug is cleared from the body, it is best to use the front half of the body when administering systemic medications.
Fluid Therapy
Since reptiles are uricotelic, that is, they excrete uric acid as the end product of protein metabolism, they are readily susceptible to visceral gout.
The patient should be supplemented with physiologic fluids at 15–25 ml/kg on the days it receives antibiotic treatment. The fluids can be given orally, intracoelomically, or subcutaneously in the lateral sinus. The latter is located at the junction between the epaxial musculature and the ribs.
Table 1. Common bacterial isolates, their pathogenicity and the antimicrobials recommended
Organism | Pathogenic† |
Acinetobacter spp. | +++ |
Actinobacillus spp. | +++ |
Aeromonas spp. | ++++ |
Bacteroides | +++ |
Citrobacter freundii | ++++ |
Clostridium | +++ |
Corynebacterium spp. | ++++ |
E. coli | ++ |
Edwardsiella spp. | +++ |
Enterobacter spp. | +++ |
Klebsiella spp. | ++++ |
Micrococcus spp. | No |
Morganella spp. | ++++ |
Mycobacteria | ++++ |
Pastuerella spp. | +++ |
Proteus spp. | ++++ |
Providencia spp. | +++ |
Pseudomonas spp. | ++++ |
Salmonella | ? to ++++ |
Serratia spp. | ++++ |
Staphylococcus spp. | +++ |
Coagulase positive | No |
Staphylococcus spp. | No |
Coagulase negative Streptococcis spp. | No |
Alpha-hemolytic Streptococcus spp. | No |
Beta-hemolytic | +++ |
†(+)not pathogenic; (+) to (++) opportunist to varying degrees of pathogenicity; (++++) pathogenic
*nn none needed; A Aminoglycoside; C Cephalosporin; F Fluroquinolone; M Metronidazole; P Penicillin
Table 2. 10 steps for rational antimicrobial use
1. Initial assessment: Always perform a proper, thorough physical examination, including evaluation of the animal›s state of repletion (starvation plays a significant role in antibiotic choice due to catabolic effects and an increase in uric acid production), and hydration.
2. Warm the animal up to its POTZ. (It is the rare case that cannot wait for the patient to be properly warmed prior to initiating antibiotic therapy.) Monitor the patient’s body (cloacal) temperature.
3. Fluids as needed.
4. Diagnostic sample collection blood for (CBC/chem, culture), urine (microscopic analysis, culture), specific specimen cultures (lung wash, cloacal or colon wash), aspirate of masses, etc. (If possible, obtain blood samples prior to fluids.)
5. Determination of method of administration (oral, systemic, topical). Coordinate your choice with owner experience/compliance.
6. Choice of drug general vs. specific, single drug vs. combination therapy; see later.
7. Adjustment of dosages (correction for dehydration, renal function, bacterial culture and sensitivity results, etc.).
8. Proper follow-up and patient monitoring (recheck and progress checks, serial uric acid measurements).
9. Author’s first drugs of choice: amikacin (caution renal patients), ceftazidime, enrofloxacin, trimethoprim-sulfa.
10. Drugs for combination therapy: metronidazole, piperacillin. Example, combine amikacin with metronidazole.