Doxycycline with or without famciclovir for infectious ophthalmic and respiratory disease: a prospective, randomized, masked, placebo-controlled trial in 373 kittens

Abstract

Objectives: The aim of this study was to prospectively evaluate in a randomized, triple-masked, placebo-controlled trial, outcomes for kittens with ocular manifestations of infectious upper respiratory disease (IURD) treated with an ophthalmic and oral antibiotic only vs those also treated with famciclovir.

Methods: Kittens were stratified into three age (1 to <4, 4 to <8 or 8-12 weeks) and two disease severity ('mild' [total disease score 1-11] or 'severe' [total disease score 12-23]) groups and randomized to receive approximately 5 mg/kg doxycycline either with placebo (group D) or with approximately 90 mg/kg famciclovir (group DF) PO q12h. Caregivers scored clinical signs once daily for 21 days. Ophthalmic examinations and scoring by veterinarians were completed on days 1 and 21. Ophthalmic and clinical resolution were defined as scores of zero for all ocular signs and all ocular and respiratory signs, respectively. Ophthalmic and clinical recovery were defined by absence of active inflammation.

Results: For kittens with mild disease, those in group D were slower than those in group DF to achieve clinical recovery (P = 0.049) and clinical resolution (P = 0.030), but not ophthalmic recovery (P = 0.064) or ophthalmic resolution (P = 0.089). Kittens with mild disease and receiving famciclovir achieved predicted 75% clinical resolution 4-5 days earlier than kittens with mild disease and receiving doxycycline alone, and kittens with severe disease (regardless of treatment group). Significantly fewer kittens in group DF developed corneal disease than in group D (P = 0.016). All five kittens whose clinical signs worsened sufficiently to be removed from the study were in group D.

Conclusions and relevance: The addition of famciclovir to standard antibiotic treatment may reduce corneal disease, length of stay and time to adoption for shelters and rescue groups, thereby increasing capacity for care. Early administration of famciclovir in kittens exhibiting mild ocular manifestations of IURD may be preferable to delaying this treatment until the disease progresses to a severe stage.

Keywords: Feline herpesvirus; antiviral medications; feline medicine; infectious disease; ophthalmology; pediatrics.

Figure 1

A total of 373 kittens entered the study and were stratified into one of three age groups (1 to <4, 4 to <8 or 8–12 weeks) and one of two disease severity groups (‘mild’ [total disease score 1–11] or ‘severe’ [total disease score 12–23]) before being randomized into one of two treatment groups (doxycycline and famciclovir [group DF] or doxycycline and placebo [group D]). (a) For the caregiver data set, no data were available on day 1 for 23 kittens. (b) For the veterinary data set, 42 kittens were censored at various points throughout the study

Figure 2

Kaplan–Meier survival curves showing the probability of achieving (a) ophthalmic recovery or (b) resolution or (c) clinical recovery or (d) resolution for kittens with infectious upper respiratory disease defined at study entry as mild (dashed lines) or severe (solid lines) and treated twice daily for 21 days with doxycycline alone (black lines) or with famciclovir (blue lines)

Figure 3

External photographs of (a,d) both eyes, and the (b,e) right and (c,f) left eyes of a domestic shorthair kitten aged approximately 4 weeks (a sibling of the kitten shown in Figure 4) on (a–c) day 1 and (d–f) day 21 of treatment with famciclovir and doxycycline. The kitten’s total clinical score on day 1 was 16; by day 21, it had achieved clinical resolution with a score of zero

Figure 4

External photographs of (a,d) both eyes, and the (b,e) right and (c,f) left eyes of a domestic shorthair kitten aged approximately 4 weeks (a sibling of the kitten shown in Figure 3) on (a–c) day 1 and (d–f) day 21 of treatment with doxycycline only. The kitten’s total clinical score on day 1 was 15; by day 21, it had achieved clinical resolution with a score of zero

Figure 5

External photographs of (a,d) both eyes, and the (b,e) right and (c,f) left eyes of a domestic shorthair kitten aged approximately 4 weeks on (a–c) day 1 and (d–f) day 21 of treatment with famciclovir and doxycycline. The kitten’s total clinical score on day 1 was 44; by day 21, it had not achieved clinical resolution/recovery (total clinical score of 15) and remained ulcerated in the left eye

Figure 6

External photographs of (a,d) both eyes, and the (b,e) right and (c,f) left eyes of a domestic shorthair kitten aged approximately 4 weeks on (a–c) day 1 and (d–f) day 21 of treatment with doxycycline only. The kitten’s total clinical score on day 1 was 35; by day 21, it had not achieved clinical resolution/recovery (total clinical score of 11) but was non-ulcerated in both eyes

Figure 7

External photographs of (a,d) both eyes, and the (b,e) right and (c,f) left eyes of a domestic shorthair kitten aged approximately 4 weeks on (a–c) day 1 and (d–f) day 21 of treatment with famciclovir and doxycycline. The kitten’s total clinical score on day 1 was 23; by day 21, it had achieved clinical recovery with a score of 2 in the right eye (which was non-ulcerated) and zero in the left eye

Figure 8

External photographs of (a,d) both eyes, and the (b,e) right and (c,f) left eyes of a female domestic shorthair kitten aged approximately 8 weeks on (a–c) day 1 and (d–f) day 21 of treatment with doxycycline only. The kitten’s total clinical score on day 1 was 14; by day 21, it had achieved clinical recovery with a score of 2 in the right eye (which was non-ulcerated) and zero in the left eye